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Update 71 (6/12/99)

Julia's Journey #71 6/12/99 T+296

June has arrived and with it a slowly but steadily improving Julia. Every day I see some new development, sometimes as small as a slightly faster turn of her head, sometimes as big as staying off the vent for a longer period of time. I look forward each morning to finding what the day's new ability will be. :-)
One obvious improvement both in Julia's condition and in our daily regimen comes from the number of medications from which Julia has weaned. Here is what she is currently taking:
2x/day Bactrim (M T W only) -- prophylactic antibiotic against lung infections
2x/day Multivitamins
2x/day Amlodipine -- blood pressure regulator
2x/day Sodium Chloride -- Yes, common table salt
2x/day Pentoxifylline -- CNS stimulator, related to caffeine
2x/day Magnesium Oxide -- another mineral
1x/day Folic acid -- vitamin
1x/day Synthroid -- thyroid balancer

Julia now has only *14* total doses of meds per day, about half of what we had to give when we were originally released from the hospital, many of them pronounceable concoctions that you or I could take (multi-vits, NaCl - table salt, Mag, folic acid). We are now able to give Julia her meds only twice per day, 8 doses at 9 AM, and 6 doses at 9 PM, rather than having so many that they needed to be administered throughout the day and night. Best of all, we have been able to discontinue the immuno suppressants such as Cyclosporine and Prednisone, and now Julia's immune system is becoming stronger. Alleluia!
I have written several times over the months about "delusions of normalcy", those brief moments when Julia would be laying in such a way, or would make a small motion, that she would look like any other baby her age. These welcome minutes are becoming more frequent. For example, Julia does not like to be awakened from a sound sleep to have her temperature taken or diaper changed. For that matter, she NEVER wants to have her temperature taken! She will very rapidly bend her legs and pull them almost all the way to her belly, great for getting the diaper off, but then straightens them out so that it's difficult to get the new diaper back on. Typical kid stuff! She loves attention, and calms when being played with or held, but cries when put down. As one of her doctors said in her clinic appointment dictation, Julia "had
a definitive temper and knew what she did or did not want done". That's our girl! Besides daily small increases in motion, alertness, and interaction, Julia has made some nice strides in the last month in breathing on her own, which opens up all sorts of new possibilities. For at least a month after our last discharge it was very difficult to get Julia to breathe more than the minute it took to suction her trach, although we tried frequently to see if she was ready... would she do it?... c'mon kiddo, take a breath... beepbeepbeep DeSat. Then, about two weeks ago, eyes wide open, she looked at us and breathed, for an hour!
Julia has been able to sprint without the ventilator for varying periods of time every day since then, when she is wide awake and generally happy. We must be very vigilant during her sprints of the "sprint-squint", when Julia suddenly squints her eyes very tightly together, and stops breathing until she desats and begins to turn blue. We now know that if we see her begin to do this squint we need to grab the ambu bag and give her a little reminder whiff, "Oh yes, breathing is fun-damental!" When Julia is ready to breathe again she takes a big swallow and proceeds to breathe normally. {***Note to other Krabbe's parents: I have never read about the sprint-squint anywhere. Have any of you seen this behavior in your children?***) We have learned that breathing consumes 30% to 40% of one's resting energy, so sprinting is a lot of exercise for a wee one who is learning how to do it on her own again. The sprint-squint is usually an indication that Julia is getting tired and needs to go back on the vent, or that we are exercising her too hard in other ways, and she does not yet have enough reserve to remember to breathe too. For example, Julia almost always desats when being picked up, but when she gets where she is going she will again breathe regularly.
Being able to get off the 5 foot tether of hose that connects Julia to the vent throughout the day opens up numerous possibilities. Julia swallows much more frequently when she is not on the vent. If you try to swallow while exhaling you will see what a child learning to swallow while on a vent is up against. Julia sometimes cries when trying to swallow while on the vent because if she does it during the wrong part
of the inspiration cycle it can be painful. It is better in her estimation to not swallow at all!

Now that Julia is sprinting and hence can more easily swallow we have been giving Julia a variety of taste treats. She prefers strong tastes, with lemon swabs being an all time favorite. She sucks and chews on these swabs in utter contentment for about a half hour until she has gnawed the cotton into a shred. When I withdraw the swab she opens her eyes in dismay and lifts or turns her head to find the swab. Julia's
teeth are right below the surface but still have not broken through her gums, so this chewing activity must feel very good. The most exciting development of the last couple of weeks was when Julia began to actively suck again, for the first time since July 1998. After lemon swabs I stick a gloved finger into her mouth, and she sucks on it as though she is nursing! This is her very favorite of all activities. If I touch the side of her mouth she immediately turns to it and opens her mouth. Julia will suck on my finger in this fashion for as long as I can sit and hold her. She prefers hours! She almost never desats during these sessions, although she needs a little extra trach suctioning. I sometimes freeze a few cc's of water in the nipple of a bottle, and then let her chew on it to make her gums feel better. The water slowly melts and drips into her mouth. She sucks and swallows repeatedly, giving me another of those delusions of normalcy, only this time it's no delusion!
Words can not adequately express how happy we are to be seeing this progress. We are in the anniversary stage of the disease: May 14th was the year anniversary of the day I discovered this disease in the library; May 29th was the year anniversary of our first MRI; June 10^th was the year anniversary of our first neurologist appointment. A year ago Julia was crying 15 hours a day, stiff always, still nursing in
between screams, but no longer gaining weight. Our family was struggling to understand WHY Julia? WHY us? Are we really helpless, or WHAT can we do? Progress on many projects stopped a year ago: our perennial garden, plans for home improvement, search for a minivan to fit the growing family, my master's degree. Many times we've had to say, "no matter" to tasks which previously seemed important, and
concentrate on what in fact really is most important.
The Krabbe's internet-work has been very important in helping us get through this past year. We learned a tremendous amount about the disease and numerous therapies, including the transplant treatment option from the families who put their stories on the net. Here is a sobering fact to contrast our knowledge base with our ancestors': On a genealogy website we discovered that my great-grandmother lost three of her first six sons, all before the age of two. My grandfather remembers his mother talking about his brothers' deaths with great sadness, believing that they died due to an unknown "poisoning", as she called it. The baby cries for a couple of months, quits eating, and dies. Krabbe's? When we first suspected that Julia had this disease we were full of self-pity for our bad luck. Now I know that in many ways our luck has been good.
We were able to meet and see many of the net families during the Hunter's Hope Krabbe's symposium last month, including CJ's folks, the first to get the word on the web. I was very excited to learn of the progress being made on remyelination by the researchers associated with the Myelin Project, as well as to see Dr. Kurtzberg again and meet Dr. Krivit, who pioneered the Krabbe's transplant treatment. Jim and Jill Kelly have done a tremendous amount to forward the general populace's knowledge of this leukodystrophy and to motivate funding for research specific to a Krabbe's cure. We owe you all a big thank you!
And of course we remain grateful to all of our friends who offer prayers and send well wishes for Julia's continuing recovery, and we send our best wishes to the newest Duke transplant Krabbe's kid, Chandler, and his family.

A year ago I was afraid of what the next year would bring for our little girl. Thanks to the help of so many good people, and to God, we can all look forward to Julia's future with pleasant anticipation.

~Julia, her mom, and her whole family

***********************
Previous journeys are archived at
http://www.krabbes.com/juliasjourney/

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Update 72 (7/18/99)

Julia's Journey #72 7/18/99 T+332

July is flying by with all of us enjoying having Julia at home. It is exciting to see some small progress every day. She is even starting to look more "normal" with the effects of the steroids wearing off. Her cheeks are a more natural size and shape, and the new hair on the top of her head is about two inches long. She is a little bit chubbier than she was when we arrived in Michigan, up from 21 pounds to 23 pounds, but she is still about the same length, 28 inches, putting her at 5th percentile in height and 45th percentile in weight for her age. She keeps her mouth closed a major portion of the time, and her eyes are open fairly frequently when awake, although she is still not a fan of bright lighting.

Julia is becoming more social. She has always had a special sensitivity to the sound of doors, but now
whenever someone enters the room they say "hi" to let her know that everyone didn't just walk out.
When someone leaves, and the door closes behind them, Julia almost always cries until someone caresses
her hair and reminds her that she is not alone. Then she visibly calms and settles. She works very hard to
orient herself in the direction of any activity, turning her head to my voice always, but then trying to go back and forth between me and the sound of other voices. She likes to listen to conversation between two people, and will slowly turn between the two, but sometimes hearing more than two people at the same time can become frustrating to her. She loves to go outside, and will keep her eyes open for long periods of time watching the tree limbs wave in the breeze against a blue sky. The only difficulty here is that she's a sweet smelling kid, making it hard to keel the mosquitoes away, so we need to restrict our outside time to when it's breezy with fewer bugs. Temperature regulation can be tricky, too. Julia maintains her temperature at about 96 F when the atmosphere around her is between 75 F to 76 F, no hotter or colder. If it gets too cold inside, we take a walk outside. We must watch her very carefully out there because she doesn't seem to sweat or shiver, so what seems like a comfortable breezy afternoon to us may cause her to either heat up to 101 F or cool down to 90 F in a very short period of time.

Julia now enjoys chewing! We have a therapy chewer, which is something like a bottle which has instead of a nipple a piece of cheesecloth into which you slip pieces of food. Julia will happily chomp on pieces of
strawberry or apricot for long periods of time. It takes her a few minutes to get used to the different way to get the taste into her mouth, first trying to suck rather than bite. But, she keeps chewing long after the fruit is taken away. She still has no visible teeth, but they are all right under the surface, and the chewing must feel very good on her gums. She really bites down on my fingers very hard when I massage her gums in the vicinity of her molars. She turns her head very rapidly to the side which is being massaged. She has developed a right side preference in most things: harder bite when right side molars are massaged, quicker to the right when turning her head, tighter right hand grip, able to move the right arm over to midline faster when doing rolling exercises.

Every day that we are at home is a good day, but we are grateful to have a major medical center nearby when needed. And, with Julia, one never knows exactly when that might be! For example, last month Julia's grandfather came to visit for a couple of weeks. The second day he was here Julia was having a great day, sprinting (off the vent), looking around, doing taste tests, moving and interacting until nap time during mid afternoon. I put her in her crib for a rest, and went to get her up before dinner. She appeared to be in a normal deep sleep, but did not want to wake up for her diaper change, nor even for the usually hated temperature probe. I picked her up, then moved her. She was limp. I took her off the vent to listen to her breathing, which was fine. In fact, she continued to sprint for about an hour. I checked her pupils, took her blood pressure, monitored her heart rate. The limpness reminded me of her symptoms when she had hydrocephalus, although her blood pressure was normal to slightly low, and her eyes remained conjugate. I called the doctor, who told me to bring her to the emergency room right away.

I began throwing all of her gear into the car when Julia's nurse arrived in time to help with transport. By this time, about an hour after I initially tried to wake Julia, she started to rouse, and then became quite normal. She had her eyes open looking around all the way to the hospital! We arrived and set up in the emergency room to wait for the results of examinations and blood draws, all the while with me wondering if I had been having a delusion when I thought I couldn't wake Julia up. I could imagine what the dictation notes for this visit would be: "Silly mom thinks deeply sleeping baby has a problem." Oh well, it would be nice if for a change something turned out to NOT be serious, even if the overreaction was a little personally embarrassing to me.

A couple of hours into our ER wait we went to change Julia's diapers, and she began urinating... bright red.
The cause of her distress was found. I bent down, kissed her, and thanked her for giving me some prior
warning so I could have her in the hospital in time, even if I had been starting to wonder if I was a little crazy. She had a very bad urinary tract infection, with no prior symptoms. It was getting worse very rapidly, and soon Julia would have been septic (infection entering the blood stream). A rapidly developing rash appeared all over her body. She began IV antibiotics, and at 3 AM we were admitted for a three day stay in the hospital. The doctors thought that the "sleepy" incident at home may have been the beginning of septic shock, although why she became fully conscious on the way to the hospital remains a mystery. I was so thankful that the symptoms were caught in time to avoid sepsis, which could have been fatal within a few hours.

Fortunately the medication took effect right away, and we were back home by the weekend with prophylactic antibiotics. We now rouse Julia at least every three hours when she is asleep, just to be sure she is able to wake up. We continue to monitor for everything, and send our blood draws in regularly, hoping to catch problems before they occur. A couple of weeks ago achieved a nice milestone. Her hemoglobin count was greater than 10. A normal hemoglobin count is usually 11.0 to 14.0, and for many months up until a few weeks ago Julia's had been hovering as low as 7.2. Any lower than that and she would need a transfusion, because red blood cells are what carries oxygen. Red blood cells must be one of the harder types of cells for new bone marrow to manufacture, because these counts are frequently some of the last to normalize after a transplant.

Julia's sats (blood oxygen levels) definitely began to improve when the hemoglobin count went up, and she now sprints for more time off the vent. What a blessing that is! One of our doctors summed this up quantitatively: Julia used to regularly desat and need bagging when off the vent every 5 to 15 minutes or so, and now, when wide awake with no other issues, will desat only every hour or so, probably when dozing. She must be very carefully monitored when off the vent, but even so sprinting gives us so much more freedom and flexibility to move around. We take her upstairs, into the kitchen, outside, down to the lake, always with pulse ox, suction machine, and ambu bag, but many more places with these three pieces of equipment than with the whole vent. Julia does not remember to breathe when she is tired, but she is getting better at it when she is awake. Toting her around gives her much more stimulation than being tied to the side of the crib. We make sure she is out of her crib with us whenever she is awake.

Last week I sent in one of Julia's routine blood draws, and received a call from the doctor's office a couple of hours later to get her into the emergency room immediately. Her potassium levels were sky high, and this could result in heart arrhythmia causing great harm. I looked at Julia, who looked back at me as if to say "Great! I love car rides!", and thought I remembered something about occasionally having errant reports of high potassium in the past, due to tough blood draws. She sure didn't appear to be in any kind of crisis, but I had no way to get a new blood sample in with out packing her and the other kids up for the ride, so off we went to the emergency room. Several hours, a set of Legos all over the ER floor, and an ECG later everything came back normal. This was the first time we ever took a trip to the hospital only to find out that we DIDN'T have a crisis, and inconvenience aside, what a nice change of pace!

It has been a good summer, although as time goes by we think often to last year. July 8th was the marker of a year since we received the formal diagnosis of Krabbe's, July 16, 1998 was Julia's most recent smile, July 17th was the anniversary of Julia's g-tube insertion. We left for Duke last July, with all the docks and boats on our lake, and the perennials coming into full bloom. Julia's favorite calming activity was to swing on the hammock, which is currently quite a difficult feat while hooked up to her equipment. Life has changed a lot for our family, but we recognize how fortunate we are to still have our littlest girl, and also that she is improving slowly but steadily every day. I still don't have any more answers to the eternal "why" question, but Julia has certainly taught us a lot about the important things in life.

Julia has made some nice progress in relearning to breathe, eat, move, and communicate, all activities we take for granted. Within the last couple of months she has become much better at sprinting, sucking and chewing, making both gross and fine motor movements, crying in multiple syllables to appropriate stimuli, but she still has a great deal to relearn. Thank you so much for your continued well wishes and prayers for Julia's ongoing recovery. Please add a special prayer for Chandler, the little Krabbe baby at Duke, who is now enduring some complications to transplant similar to what Julia experienced. All of these kids go through so much for the goal of survival.

~Julia and her mom

******************************************************************

You can find previous Julia's Journeys archived at
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Update 73 (9/06/99)

Julia's Journey #73 9/6/99 T+12 MONTHS!

Yes, it's true, we've passed the one year anniversary of Julia's transplant! This summer has flown by, the kids are back in school, and Julia has made progress in many ways. Open eyes, graceful motion, new teeth, even some one sided smiles are now part of her repertoire of new tricks. Our days are filled with physical therapy exercises, new flavors to taste, and responding to Julia's open eyed requests for attention.

Julia now moves so much that we needed some sort of sedation to ensure that we would get good images on her MRI at the end of July, images which would be uselessly blurred if the patient were in motion during the process. We were quite concerned about giving Julia the standard sedative used for this purpose, Chloral Hydrate, because in the past she became over sedated by even tiny amounts of the drug. This time we tried 2 mg of Versed intranasally, and it seemed to do the trick. Julia had been crying a lot during clinic before the MRI. After she received the Versed she became very "happy", then fell readily asleep, tired from the exertions of the day. She flew through the MRI with no crying, awakening as she was wheeled out of the MRI room, and was very happy and alert afterwards on the way home. We witnessed what appeared to be the beginnings of a smile in the car on the way out of the parking lot.

At first I didn't believe that this could have been an intentional smile, since Julia's last previous smile was on July 16, 1998, more than a year earlier. But, a couple of days later, when I had Julia sitting on my knees and looking at me while I supported her under her arms, while I was rocking her around so that she could practice righting her head (she's now quite good at this), there it was again! The left side of her mouth curled upward in a little half grin! I shrieked with delight, and called everyone in the house to come see. Julia grinned at us several times that night. Her smiles are becoming more frequent, although still only on the left side of her face. Usually they are precursed by a multitude of other facial maneuvers, but always are accompanied by wide eyes, and indicative of a happy state of mind.

Julia has gained much strength in the last several weeks. Dressing her is getting easier. If I pull one of her arms up while she is laying down to put her hand through an armhole, she will sit right up. While she is in her Panda stroller she will sit up fully away from the back of the chair. She will sit on her own with just my hand supporting her lower back. While she sits she moves her head back and forth as if to scan her surroundings. Sometimes her head will hyper extend backwards, or fall forward to occlude her trach, but with a little jostle she will right it again. We are now working hard to get her to lift her head off of her shoulders more often, since she still assumes a resting position with her head on her shoulders.

Julia's movement patterns have become much more graceful. When she awakens, she does a full body stretch that is grace in slow motion. Her legs bicycle several times, head moves back and forth, arms bend and extend, hands open and shut. I thrill to look at her hands, which no longer fist! Her thumbs still have extra tone, but they now do not ever retract into her palms, and most often appear as any other child's hand at rest. When we place an object in her hand, particularly one with a lot of texture, she closes her hand around it for a while, until she forgets about it, when it drops. She wiggles her fingers when we tickle her palms, which is so exciting, because formerly we couldn't get her thumbs out of her palms to even begin to tickle in there.

All of this motion has brought forth two new situations. Julia's feet now move all the time, but she for some reason turns them 90 degrees to the side and up, exactly the opposite of what the Krabbe's usually makes kids' feet do. The turning is so forceful that it is very difficult to make her feet return to a normal face forward position. We will soon receive splints to help correct this, but don't mind, as we know that in an odd way the turning is indicative of improvement. The other situation is harder to control. Julia is much more active on the right side of her body, everything below her face, which is more responsive on the left. She pulls to the right so strongly that her back is beginning to "C", and little creases on the right side of her tummy are beginning to form. We work very hard to get her to look midline and left, and are making some progress. But, she has surprised some nurses who know to position Julia laying left, looking left, with pillows to keep her left, and then to walk away to attend to other matters, and turn around to find Julia looking to the right -- RIGHT at them! :-)

Julia received a bit of Transplant Anniversary cake on August 20th, baked by her big sister to celebrate the big day, but she had to gnaw away at this taste treat with swollen and sore gums, due to an ongoing lack of teeth. We have been rubbing her gums with gloved fingers, Nuk toothbrushes, wash cloths, and everything else for weeks. Julia even enjoys her own thumb. When someone bends her arm so that her thumb is near her mouth she turns her head toward it and opens up, ready for a good chomp. She will suck on her thumb in the same suck-swallow-rest cycle as a newborn for hours, until she falls asleep, as long as someone holds her arm in the right position. When you let go of her arm it extends enough that she can't reach it, and she cries, MULTI-syllable whales. She sometimes even closes her lips around her thumb, making big smacking noises, although she can't yet maintain this practical position for very long. She can handle small amounts of frozen water or breast milk in a syringe or nipple, and she also loves to munch on fresh fruit in a cheesecloth. But, still no relief for the swollen gums, until...

August 29th, Julia cut her first two teeth, just 20 months and 2 days old! It had been a struggle, but we proud parents are happy to relate that her two bottom dentures have arrived, and that they are firm, straight, and sharp! I think that the big event surprised Julia even more than it did us. She keeps sucking her bottom lip over them as if to see what it is in there that is causing this new sensation.

Julia has now survived cold #2 without going into the hospital. She came down with it the first week in August. The main problem was the copious secretions, and the fact that we couldn't sprint her off the vent. Shortly before she acquired the cold she had been sprinting many hours on some days. When the cold began she could not sprint at all, although the rest of her cognitive functions seemed to remain intact. We were not able to get Julia to sprint until about a week ago, although she has gone back to it even better than before, with a new twist. For the better part of the last year if we gave Julia extra oxygen she would apparently think she had all the O2 she needed, and forget to breathe at all. Desats into the 20's and 30's were common. We tried it again, off the vent, and she has apparently completely passed this stage! For the last several days she has done several hour stints of breathing completely on her own, without the vent, with just a small amount of O2 (3/32 liter, or about 23% O2 vs. the standard 21% O2 in room air). It is very helpful when doing physical therapy or transporting Julia around the house to be able to leave the vent behind. We can even go outside and swing on the hammock with oxygen in tow, if we don't have to carry the vent. Discontinuing the vent is a main goal, and being able to sprint is a big step. We have a long way to go before we can do away with the vent, especially when Julia is dozing or sleeping, and particularly when she has any kind of respiratory infection.

Julia received a visit from her six cousins the second week of the month. This would be the first time since before diagnosis that Julia would have substantial kid-company, just for the sake of visiting, not in a clinic or hospital. We worried about germs, but strictly enforced the hand-washing policy, the shoe-removal policy, the keep-the-door-closed-so-the-bugs-stay-out policy, and held our breaths waiting to see if all of our precautions would be enough to prevent germs from spreading. Julia LOVED all the attention, and really benefited from hearing extra voices and commotion. She gave Cousin Dez and Aunt Cheryl left-sided grins before they went home, and learned to really preen when someone was combing her hair, which happened frequently. Julia lifts her head backwards, closes her eyes, and purses her lips as her hair is stroked and stroked. This was such a popular activity that once again her hair is thinning at the temples, only this time with a good cause. It is long enough now that we can put barrettes in the top, which look cute, and slow the combing down. A new thicker down is appearing under the current hair. We are waiting to see what color it becomes. Julia's hair began light brown with copper tones, but the last set of eyelashes she got, in mid August, her fifth set, are black.

There appeared to be no negative immune system fall out from the visitors, so we are hopeful that as the kids start school, Julia can overcome any germs they bring home. We will be having Julia's one year studies done in the next several weeks. We are cautiously optimistic that if the results show an improved immune system we can finally emerge from our cave to take Julia out (within reason!) to see the world. The MRI results have come back, showing no new abnormalities, and some hints of improvement. Julia's blood work done the day before her 1 year transplant anniversary showed her to have, for the first time in a year, NORMAL hemoglobin levels of 11.1.

We can tell by Julia's actions and her appearance that she has improved immensely in the year since she underwent transplant, but we remain mindful that the next year will be equally challenging. Julia still needs to remember how to do some very basic functions, such as breathing and eating. We have come a long way through some very difficult times, but look forward to meeting and overcoming the next challenges in the upcoming several months. Transplant is definitely a multi year procedure! Our lifestyle with a child who has multiple physical difficulties is far different than it was before we began this journey, but we are still glad that we had the opportunity to give our little girl a chance to live. We thank you, as always for your continued well wishes and prayers.

~Julia, her mom, and her whole family

Previous journeys are archived at
http://www.krabbes.com/juliasjourney/

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Update 74 (11/14/99)

Julia's Journey #74 11/14/99 T+15 Months

The leaves are gone from the trees, the boats are off the lake, winter is around the corner and we're elated to be at home to see it happen! Last year at this time we were still in the hospital in the midst of our fight against hydrocephalus. This year Julia is home and happily getting just a little better every day. She is developing a definite personality full of both kisses and love, and some temper too. We are also seeing some of the autonomic functions returning and getting stronger, sure indications that her central and peripheral nervous systems are slowly repairing themselves. And, there's a whole lot more of Julia to love. She's now up to 27 pounds, 30 inches long! That puts her in the "under-tall" category, as one of her nurses says, every inch huggable. Everyone keeps saying she will narrow out when she's moving more and breathing more on her own, both of which are happening, but it's hard to detect much in the way of narrowing.

Some of Julia's best progress has been in the category of speech therapy. We have been told that many children who can not eat for long periods of time develop aversions to food. Not Julia! Julia has learned how to suck again, and does so in a newborn nursing pattern of suck-swallow-rest... repeat. The trick to this appears to be gently pushing her lower jaw up so that she can form a seal around a nipple. Her swallow is still delayed, so some saliva can still pool in her mouth and go down her windpipe. We keep the suction machine handy. But, frequently, after she really gets going, she can actually take some liquid from a nipple. Her record to date is 15 cc's of juice frozen in the nipple. The cold stimulates her to suck, and the juice melts slowly enough that she can handle the quantity. She loves it!

The juice is inconsequential when compared to Julia's newest taste treat. Alison and Cameron donated some large chewy sweet-tarts from their Halloween baskets to Julia. At first she wasn't too sure about the taste, but then she was coming right out of her chair to get more! It takes her about an hour to eat one, but she will suck and chew and smack her lips until we have to put the pieces in a piece of gauze so she can have more. Her lips and tongue turn purple, and she takes on the appearance of most other kids her age. After one of these sessions we give her a nuk, which we attach to a trach collar so she can keep it in her mouth. She will keep sucking on the nuk for hours afterwards. It will be a long time until her eating skills are good enough that we do not have to rely on the g-tube for the majority of her nutritional intake, but the fact that she enjoys eating and can swallow albeit sporadically is very much in her favor.

Julia is making more and more facial expressions. She smiles sporadically. We will see her smile for a few days, then forget all about it for a few days, then more smiles a few days later. When functions first return, they are weak at first, then disappear for a while, only to come back a tiny bit stronger the next time. This can be frustrating, because each time something disappears it is reminiscent of the first time everything disappeared. But when a function comes back stronger the next time it is true joy.

Julia continues to open her eyes for longer periods, and to hold a steadier gaze. She was checked last month by the eye doctor to determine how much sight she might have. Julia's optic nerves are very pale, indicative of substantial demyelination. Yet, there is some yellow to them, indicating the possibility of some sight. The eye doctor suggested three things that kids with other conditions resulting in similar optic nerves report that they can see: Christmas lights, TV, and ceiling fans. Julia's crib is now rigged with all three. Special thanks to Terry and family for the custom size TV! :-) On Halloween night we saw proof positive that Julia has some vision. She would blink at the flashes going off as we took pictures of the kids in their costumes. You can see one of these pictures in the attachment.

Julia's temperature regulation mechanism seems to be getting better too. We still have to keep the room temperature between 75 and 77 degrees, but if it is, and if there is no breeze, and if Julia doesn't have a cold or other bug, she will now generally maintain her temperature above 96.5 F. This is much improved over the 93's F and 94's F that we used to see! It used to be hard to judge her temperature by the feel of her skin because for months she did not sweat or shiver detectably. Her heart rate was the most reliable indicator if a thermometer wasn't available. About a week ago this changed. Julia started to sweat! A couple of days later one of her nurses noticed some goose bumps after a bath! Julia definitely prefers warm, and will cry if her body temperature goes below about 95 F. She calmly rests her hand in a bowl of warm water, but rapidly retracts when her hand is placed in cold water. Her legs go flying when her bath water is poured on her, especially if it is the wrong temperature.

Julia's breathing is improving. She has been going for several hours at a time off the vent, with no desats whatsoever, usually with just a tiny whiff of oxygen supplied through her trach collar. When Julia is wide awake, with no cold or other bug, and in a stimulating area, she now happily breaths virtually without assistance. We need to be very careful about this though, because we never know when something will suddenly pop up. During a recent visit to the orthopedic surgeon's office, Julia was breathing very nicely, when she just quit, for no apparent reason. She was happy to do everything else, especially make facial expressions and move around in her stroller, but she acted as though she had never breathed before, and had no intention of ever doing so again, for about 4 hours. By the next day she was more like normal, but why she had this complete apnic spell remains a mystery. Overall Julia's progress in breathing on her own is very good. Another indication that we have had significant improvement is that now when Julia is suctioned, she inhales strongly, even creating squeaky tires sounds. This is a much more normal reaction to having someone sucking all the air out of someone, which is what happens when a trach is suctioned. A person who breathes normally will try to inhale some of that air back.

I experienced this first hand recently when I went to the dentist, and the hygienist came after me with a yaunker, the device used to remove saliva during dental procedures. Julia has one just like it at home. I nearly jumped out of my seat thinking about the three or four thousand times I have suctioned her and little of what she must go through. Now she bites down on the yaunker fiercely and clamps her lips around it, refusing to let go. This is even more fun now that her first upper tooth has finally poked through. She bites very hard, so that I can even pull her up several inches off of whatever she's laying on when she decides to play this game, just by trying to pull the yaunker out of her mouth.

We have completed many of Julia's annual post transplant tests. Julia's cerebrospinal protein count at the time of her transplant in August 1998 was 152, with essentially the same count of 148 in January just before we left Duke. The average person's is somewhere between 20 and 40. The high count in Krabbe's kids is caused by the missing enzyme not carrying away the byproducts of myelin development, which show up in this test as elevated protein. So the lower the count, the better. Now Julia's count is 119, not yet normal, but a statistically significant step in the right direction! And, as of her neurologic exam, she exhibited all of her basic knee-jerk reflexes, although still small and slow. But, they're there! On July 8^th, 1998, the day of her diagnosis, she had *none*.

Julia's usual blood work has all neared normal as well, except her Thyroid Stimulating Hormone, which remains high (she takes Synthroid to counteract this). The good numbers on her basic chemistry counts and complete blood counts allow us to do blood draws less frequently. Unfortunately Julia's port clogged again after her annual tests, so she had to have the old one out and a new one in a week and a half ago. We always fear that she will loose some ground every time she is put out for surgery. Once again she had the minimum of anesthesia, just a few whiffs of isoflourine. She was wide-eyed by the time she was in the recovery room! But, there have seemed to be more residual effects this time than after some of her other surgeries. Her groin was poked multiple times to look for port veins there, leaving her black and blue and unable to do much physical therapy for the week after. (Ultimately the port was reinserted back into the same spot on her chest where the old one was.) Julia was more sleepy for several days, and more apnic, with less swallowing. She is just now getting back to her pre-surgery self.

Every day is new and different with our Julia, as we move back to a more normal lifestyle. I can't help but feel some sadness when I see the bundle of activity that other toddlers Julia's age exhibit. I automatically experience pangs of "Why can't my little girl jump and yell and laugh?" But, there is no greater experience than watching her regain some of the most basic functions that we have seen recently, such as breathing, swallowing, smiling, sweating, open hands, open eyes. Today we practiced massage therapy with her, and she was so happy, kissing repeatedly, a joy to behold! My overwhelming thought is that most of us have all the abilities she lacks, yet frequently, despite our overall good fortune, we consider ourselves or our lives deficient in one way or the other. Our experiences with Julia have taught us a great deal about true good fortune. The Beatty Thanksgiving will be a very happy and grateful one this year, and we wish the same to you.

~Julia, her mom, and her whole family

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Julia’s Journey #75 2/5/00 T+536

Greetings to all on the occasion of a prominent anniversary for Julia. It has been one year since Julia’s med flight from North Carolina to Michigan. We have come so far! Good fortune plus diligent hand washing seem to have paid bountiful dividends. Julia’s last hospital stay was in June, almost eight months ago.

Thanksgiving and Christmas flew by. Julia really enjoyed the sights and sounds of the holidays. We decorated our tree in red and white lights, since red is the color she is most likely to see. Alison and Cameron were concerned that Santa wouldn’t leave any presents this year because Julia resides in the living room, and has been known to stay awake at night. No problem though, Julia must have tripped Santa on his way up the chimney, because he certainly dropped a lot of presents by the fireplace for her and her siblings. One of the most useful is Julia’s mini recliner, which gives her a new and very practical place to sit and survey household affairs. Attached you will see a picture of Julia in her Christmas finery.

We rejoiced to have Julia at home on December 27^th to celebrate her 2^nd birthday. What a difference a year makes! On her first birthday we were in room #5212 on the Duke transplant floor, wondering if she would survive the night, one of her worst. This year she sat on my lap at the dining room table, while her brother and sister helped open her presents. Thankfully, the coming of the year 2000 was as uneventful here as it was for the world at large, merely the changing of the calendar. After the excitement we endured in 1998 and 1999, it was a pleasant change of pace.

Julia continues to progress in different areas at varying rates. At her neurology appointment in January, Dr. Leber congratulated us on having reached one of the goals we had stated during the previous visit. Last August Julia was on the ventilator 24 hours per day. She is now OFF the vent twelve hours per day, as long as she is not sick. She still takes a tiny amount of oxygen, 1/16^th to 1/32^nd of a liter, a few extra molecules per minute. Her oxygen saturations are in the high 90’s with the O2, and in the low 90’s without it. Although this is a very small amount for a more normal person, it seems to make a big difference to Julia.

Julia keeps her eyes open more frequently than in the past, not all day, but virtually always when she is upright. Although she continues to prefer low light levels she opens her eyes in bright light if there is an attractive sound. She likes to watch her Baby Mozart tape in a darkened room, and works hard to orient her head toward the TV. Many of our nurses have commented on how she follows me with her eyes. It takes 7 or 8 seconds on average for her to move her eyes in a full sweep from right to left or back, with the movement being very jerky. She fixates with a steady gaze more often. I constantly try to ascertain how much she can perceive. Up until recently she would not react when her eyes were wide open if I put my hand right in front of her to occlude her view. Now she reacts with nystagmus, not the desired response, but still a response.

Julia’s hearing remains acute. She especially enjoys one new sound, her own voice! Because of the trach bypassing her vocal cords she is vocally silent when she is off the vent. When she is on the vent she can make sounds upon inspiration. She sounds just like a lamb: baaaaa... baaaaa... baaaaa. We can tell that she very much enjoys this game. She also lets us know immediately if she is unhappy, with a quite normal sounding multi syllable cry. She has a sweet little voice! We are exploring the possibility of a special valve that she could wear during the day that would allow her to hear her voice more often.

Julia is able to sort noises that merit attention from noises to be ignored, much better than she could earlier. In the past she startled with every closing clipboard, every spoon on a plate, every pound of a foot on the floor. She still startles, but much less readily. For several months it was very difficult for her to fall asleep, because she constantly startled awake to the slightest internal or external signal. For the last month or so she has settled quite well into a normal two year old schedule.

The most exciting progress has been with Julia’s head control. For so long lifting her was like lifting a newborn. We had to hold her head and carefully be sure that it didn’t flop back or to the side. Now, she holds it all by herself so well that we don’t worry about it! When she is doing tummy exercises on the therapy ball she can hold her head up for about a minute in a position similar to a crawling toddler. She moves her head from side to side quite readily. She still prefers the right side, a source of concern because she has developed a 40 degree scoliosis. We are seeing more initiation of left sided movement, especially when stimulated. Our next big challenge is for Julia to make the connection that she can reach and grab. We have seen a lot of new leg motion, but not nearly as much arm motion. One of our therapists theorizes that the weight bearing Julia does in her stander is stimulating neural pathways in her legs, so we are working on developing weight bearing arm exercises, not so easy with the trach! Our efforts may be paying off because just this past week we have been seeing more bent arms and arm rotations.

Julia continues to hone her eating skills with various frozen juices in nipples, and now with yogurt. Her swallow is delayed 7 to 10 seconds, so she does better with foods of higher consistency that give her tongue more feedback. We have noticed a pattern in the length of delay for responses. It takes 7 to 10 seconds to swallow, move her eyes across a field of vision, initiate a rolling response, react to warm water poured over her, and many other mild stimuli. In contrast, she reacts almost immediately to unpleasant stimuli, such as a painful poke, loud clap, or something very cold. Thankfully, she once again exhibited all reflexes at her recent neurology visit, as well as a few extra ones on the side opposite from the stimulus. :-) She habituates to stimuli rapidly. We are likely to get a response to most things, but once she has reacted she is ready to go back to rest.

We have been fortunate to have had no major medical challenges over the holidays. In December Julia caught a cold, and survived it with a few albuterol treatments, some extra vent time, and no hospital. In January her port clogged, a g a i n. (Oh, this story is so old!) Now we can not draw blood at home, and monthly labs have to be done by finger or heel pricks. We hope to resolve this issue soon. The only other problem has been a Clostridium difficile infection, essentially an overgrowth of bad bacteria in the gut due to too many antibiotics. Julia has been on Bactrim since a year ago, first for pneumonia prevention, then for urinary tract infection prophylaxis. Now she is on Vancomycin, another very powerful antibiotic, to fight the clostridium, in addition to the Bactrim. I am hopeful that she can avoid another Clostridium difficile infection until the Bactrim can be removed permanently. Julia continues growing rapidly both in height and weight, soon to catch up with her age peers. One area she lags behind in is head circumference, which has not grown any larger in the last year, but hopefully soon this will begin to catch up too. We know that the neural pathways are growing because she does so much more than she did a year ago, but she still needs a very substantial increase in white matter to avoid permanent microcephaly.

As always we are grateful for all of your well wishes and prayers. Julia has come so far, and although the road ahead is very long, we know that she will exceed everyone’s expectations. We are pleased to hear that a number of other Krabbe children have been transplanted recently at Duke, and wish them great success.

~Julia, her mom, and her whole family

Julia’s Journeys are archived at

http://www.krabbes.com/juliasjourney/ 

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Update 76 (6/25/00)

Julia's Journey #76 6/25/00 T+676

Thank you to all who have inquired how Julia is doing. Julia is doing a little better, continuing to improve slowly on many fronts, and making some nice strides in specific areas. She has now been out of the hospital more than a year, with the exception of a brief two day stay in April for some wheezing which may have been allergies or asthma.  Fortunately the wheezy symptoms are gone, and our girl is now breathing very well, still on a whiff of oxygen, but without the ventilator except when asleep. Alleluia! Why the tiny amount of oxygen? Nobody knows.  Julia sats in the high 90's with the faintest whiff, and low 90's without it. I keep working on weaning her, because the oxygen tank weighs about 10 pounds, and with Julia at 32 pounds, that's an extra 10 pounds I don't want to carry on my back as we stroll outside. Julia has grown out of her stroller when the vent is attached, so being able to take her places with only an ambu bag is a major goal.

She is doing very well at coughing and has even started sneezing every so often. When she sneezes she looks shocked, "WHAT happened?" Who would have believed that I would enjoy the looks of a "snotty nosed kid", one who can sneeze herself! Julia seems to look forward to suctioning. When the machine is turned on she gives kisses. She must recognize that it feels good to not have all that gunk in there. If she becomes adept at getting the mucous up ... and she remembers to breathe ...maybe someday she won't need all this machinery- whoaaaaaa, what exciting thoughts that several months ago I would not have voiced out loud. Julia still undergoes bouts of hiccups every two to three weeks during which she hyperventilates, which makes her body think she has enough oxygen for a few hours, during which time she doesn't take a breath. She also occasionally does a big sigh, and then doesn't take a breath for 20 to 30 seconds, but will resume breathing normally on her own after hitting a sat low of about 80.

Julia still has the same size trach tube that she did when it was first put in a year and a half ago, so there is plenty of room for the air to move past the trach, through her vocal cords, and through her mouth and nose. Her vocalizations are very sweet, or if crying, very loud, but unless we hold our finger over the trach intake not enough passes her vocal cords to make her audible, unless she is on the vent. Hopefully we can get a Passy-Muir valve this summer so she can talk all day and all night if she wants to. Her hearing is so acute. Making vocalizations is very rewarding for her, but it's not worth keeping her on the vent so that she can hear herself.

We still do not know how much Julia can see, but she now often looks towards events she notices. The biggest key to keeping her eyes open is keeping her upright. When she sits on my lap or is doing exercises her eyes are usually open very wide. There is continued improvement is steadiness of gaze and decreasing nystagmus, and she will orient her eyes at the midline if she is sitting facing me directly. Midline or down are the hardest directions for her eyes to look. Her pupils are now very close in size, and both eyes are nearly always on the same plane. Visitors who have not seen Julia for some months are always surprised at her wide-eyed alertness once she is accustomed to them.  Julia always goes through an initial possum period when she meets new people. She appears to pass out and won't interact until she has heard their voices for some time and is sure that she won't be poked, pinched, or prodded. I can tell that she is awake because I can see the rapid eye movement under her closed lids, but the casual observer always says, "She's asleep." It's quite convincing, limp arms and all. After a few minutes she will peek with one eye, then a couple of kisses, then she sits up and gets involved in the conversation. This little act is at its best when we visit her neurologist, where Julia likes to hold out until after the doctor leaves the room. We spent the entire last appointment bouncing her, jiggling her, only to have her look like a sleeping Raggedy Anne on a floppy day. Our nurse laughed out loud when the door closed after the doctor left and Julia opened both eyes bright and wide and tried to sit up. She has developed quite a personality, full of temperament! 

Julia's head control astounds me. We go "driving" on the hammock. I sit her on my knees and hold only her hands. We rock and sway and move all over. She can maintain her head control at almost all angles, and works hard to keep herself upright by hanging tightly on my hands and pulling hard with her arms, which are becoming quite strong. Our next big goal is for Julia to reach out and grab something. It hasn't happened yet, but in the last month or so her arm movements have improved dramatically. She now moves them frequently by bending them at the elbow and pulling them forward. She does this at the sound of my voice, so I put her arms around my head and thank her for the hugs. We have new elbow splints to help keep her arms straight while she does weight bearing exercises on them. Weight bearing seems to be the key to activation. The more we do on arms or legs, the more she moves her limbs independently. It is fun to hold Julia under the arms and tap her feet to the floor when her hard foot splints are on. She tenses her legs and "stands" on her own for a few seconds. 

Julia's rolling is sporadic. Some days she does very well, and with just a little help holding her hips she will roll by herself from her side onto her stomach. Other days she looks at you as though you are asking her for advanced calculus. Last week at therapy was one of those days. We rolled her on her stomach and let her lay face down with her cheeks resting on her hands. I stood up to mark the calendar for the next week's visit, and Julia pushed her head up to look at me walking away! She can do this up to four times in a row now, giving me goosebumps of joy every time. And, speaking of goosebumps, Julia is now adept at both sweating and goosebumps, both of which had disappeared for many months, reappearing a year or so after transplant, but now appearing nearly normally. Her temperature regulation is still not perfect, but it is much improved.

She loves to sit up, and is activating her trunk muscles more and more so that she can sit with only minimal help when she is so inclined. She especially likes trying to sit up when she is in her crib and someone walks by without paying any attention to her. She did this last week and went all the way forward, landing face first in her tray of combs, brushes, and thermometers. She looked shocked and started to cry! I was shocked too, only I laughed for joy. Julia's kyphosis (humpbackedness) and scoliosis (s-curve to spine) are quite pronounced. She just received a back brace to help her sit up without making the curvatures worse. She looks, dare I say it?, nearly normal, sitting upright on a bench, pigtails in hair, feet dangling, looking around with big bright eyes, with the back brace helping to keep her back in the right position. The brace is new and quite uncomfortable for her so far, because she's not accustomed to being stretched out in her Star Wars Storm trooper's armor. I know that once she's used to it this is going to be a major step forward in integrating her with the rest of family life. She can sit up tall with this brace and be part of everything we are doing for as long as she can tolerate it. 

Julia is improving her ability to communicate and interact with others.  We play "Where's Mama?" She seeks me out by looking in my direction. She is starting to seek others too, including Daddy and some of her favorite nurses. Her smiling is improving with the record thus far of 10 in one day. It is not easy for her to make a smile, and she goes through a variety of facial motions before accomplishing one. She smiles, looks in the direction of who she wants, and raises an arm when she wants to play. She loves to be held, and gives multiple kisses when happy. She shows surprise with wide eyes and open mouth, and knits her brows when making effort. When she is working at exercises or just the effort of sitting up she forgets to close her mouth, so it hangs open.  If we get right in front of her and tell her to "close your mouth" she will, sometimes needing a gentle touch to the lips as a reminder. She cries if others are sad, and smiles when others are happy. Her brother loves to play with her to get those smiles, and she loves it too. When he finishes and walks away she will sit forward in her chair and look after the direction he went, sometimes crying. She is a joy to hug and hold, and those smiles are more beautiful than any movie star's. They are hard to catch on film, but I hope to have one to put on the net soon. We have to work hard to keep Julia's sleep schedule optimized.  She still gets her days and nights mixed up occasionally. We want her to sleep at night so that she can stay awake during the day and take advantage of all the stimulation we want to give her, but as with all two year olds, she has a mind of her own.

Taste testing is one of Julia's great joys in life. We've branched out to tastes of anything with color (to see if it goes down her windpipe).   Popsicles are her current favorite, the kind that come in the thin long plastic bags. Julia has at least parts of about 20 teeth now, which she frequently grinds with a loud noise, and a very strong bite. Fingers beware! So far her teeth are quite straight. She loves to suck on her nuk with a loud smacking noise and lots of motion similar to the cartoon character Maggie Simpson. When we help her get her hand to her mouth she always orients her head to her hand and opens her mouth ready to suck her thumb. She still needs help keeping both the nuk and her thumb in her mouth, but would happily suck, munch, or eat as long as we help her keep whatever is in there in place. Our therapists tell us that many children with trachs or vents who have had multiple procedures become orally defensive. Not Julia! She loves to sniff, especially vanilla, fresh mint from the garden, and citrus, and especially to taste, which makes her smack her lips in delight. Her swallowing is faster and more consistent, but still not good enough for any substantial intake of nutrition.

Julia has remained on the same amount of food, 600 cc's a day, since she received her g-tube almost two years ago. She is not gaining much length, only about 8 cm in the last year and a half, making her very short for her age at 78 cm. Her head circumference also continues to lag, gaining only about 1 cm since arriving back in Michigan. She has gained almost 12 pounds in the same amount of time, making her quite rolly poly. She only receives about 475 calories per day. We want her to have the maximum nutrition in her tiny dose of food so that her neural development can be optimized, but we don't dare give her any more calories or she'll burst sideways out of her equipment. She receives 20 ounces of human donor pasteurized milk, the first kid ever approved by the state of Michigan to do so (as of last week - it CAN be done!), two ounces of neurotoxin-free, bacteria-containing organic yogurt to ward off clostridium, and 1 1/2 ounce of cranberry juice to prevent urinary tract infections. She still receives supplements of sodium and magnesium, prophylactic bactrim, pentoxifylline as a CNS stimulator, folic acid and multivitamins. We've heard that breathing on one's own takes 30% more energy than breathing on a vent. Julia is now breathing on her own most of the day, but this form of diet plan doesn't seem to be working. Hmmm, I guess she'll have to get on the treadmill soon.:-)

Julia and I will soon be going on her first big trip since returning home from Duke, to the Hunter's Hope Krabbe's Symposium in New York. To those of you who will be there, we look forward to seeing you, and to everyone else, we look forward to giving a great report about Julia's trip.

~Julia, her mom, and her whole family

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Update 77 (7/11/00)

Julia's Journey #77   7/11/00   T+692   Symposium Synopsis

Two updates so close together!  Yes, it's true, because of the great excitement we experienced at the Hunter's Hope Symposium.  Julia did very well overall.  She slowly acclimated, first to the 6 hour drive, then to being around new people in different surroundings.  We were fortunate to be able to bring one of Julia's home nurses with us, so that I could attend the symposium during the day, and Clara could tend Julia at night.   Coincidentally, I grew up just a few miles from the conference center.   We arrived in New York a day early to visit with my relatives, some of whom Julia had never met before, others who had not seen Julia since before she was diagnosed.  Rob, Alison, and Cameron had a wonderful time staying at my sister's house with all the cousins, and visiting the local attractions including Fort Niagra and Niagra Falls.  We feel lucky not only to have a wonderful organization dedicated to raising funds to research the disease that our daughter has, but also to have it located in my home town.

Julia sat through every presentation of the three day period.  Initially the clapping and door latch closing in the conference room made her startle and cry, as did the clanging of silverware and ceramic plates in the dining room.  By the end of the conference these sounds no longer bothered her.  At first Julia would "possum" when a new voice introduced itself.  She closed her eyes and did her limp act, anticipating a doctor's poke, pinch, or prod.  By the end of the weekend she was alert and content to meet every individual.  She blew kisses to the Krabbe's moms who held her, and especially to the siblings who said "hi".  She loves kids' voices.  Kelly Sroczyk, David's mom, with whom we became good friends with in Durham, even saw one of Julia's smiles, a phenomenon that Julia bestows on only her very favorite people.  Happily, everyone else was very tolerant of Julia's frequent suctioning.  She stayed awake almost all of the time we were in seminars, roughly from 8 AM until 6 PM.  When Julia is awake she does a lot of swallowing.  Most of her saliva goes down her esophagus, but some still goes down her windpipe.  All that wakefulness caused a lot of swallowing, which caused a lot of suctioning, which caused a lot of noise.  Thanks to everyone for being patient with the noise.   Julia's only problem of note was a case of hiccups during breakfast on Sunday morning, causing the customary hyperventilation and subsequent lack of breathing.  After an hour or so of artificial ventilation Julia was breathing on her own again.   I was worried that Julia would play possum for Dr. Kurtzberg, her transplant doctor, but she opened her eyes, did a few head control tricks, and threw a few kisses.  I will send pictures at a later date.  This email is so long as it is that I don't want to overburden the receiving computers.

Two years ago when Julia's transplant experience first began at Duke four Krabbe's families came together and discussed a number of directions we wanted to see Krabbe's research and activism go.  Many of topics we talked about then are actually in the works due to Hunter's Hope funding.  I have had numerous questions since returning from the symposium, and know that everyone is curious about what is happening in research.   Below is a  summary of what I learned about the progress being made to fight Krabbe's and related diseases.  I apologize to you and to the presenters for any errors contained herein, remember, I'm not a scientist, just a med-mom, and some of these words aren't in my dictionary.  My objective is to provide a thorough overview that explains some fairly complicated concepts in understandable terms.  I invite all the doctors and other parents who were at the symposium to email me with any comments, suggestions, corrections or important points that I missed.  There is a tremendous amount of information here, making for a long report, but the length is a happy indication that substantial progress is being made.

Scientific Summary

Background:  Myelin is the sheath that surrounds neurons so that messages transmitted stay on course.  Myelin is similar to the black rubber of telephone lines that surrounds the metal wires (nerves) inside.  When myelin is manufactured there are waste byproducts.  The enzyme, GalC, is needed to carry these bad byproducts (galactosylceramide and psychosine) away.  In non-Krabbe's individuals this enzyme, GalC, is created in the marrow and circulated throughout the body.  In Krabbe's kids, the gene telling the body to create GalC is defective.  Without the enzyme the waste products build up, forming globules instead of straight myelin sheaths, interfering dramatically with the transmission of neural impulses.  This has been compared to not taking the household garbage out, no problem at the beginning, but eventually the house is overloaded.  Scientists are researching four possible ways to cure Krabbe's.

• enzyme replacement therapy
• gene therapy
• bone marrow transplant
• stem cell therapy
Terms:
• Murine -- having to do with mice, not red eyes :-)
• Twitcher mice -- mice that are missing the same enzyme that Krabbe's kids are missing.  They twitch uncontrollably as their disease progresses, hence their name.
• Myelin --  from the Greek word myelos, "marrow" (akin to mys, 'mouse', BTW).  Myelin is the white matter at the core of the brain.  It is sheathing material that surrounds neurons.
• GalC -- Galactocerebrosidase - {pronounced 'galacto - cer - eee - bro - side - ace'}, the enzyme that is missing in Krabbe's kids. This is the good stuff that you want more of.
• Galactosylceramidase and Psychosine --  the waste products that build up causing the globules that short circuit the nerve impulses. This is the bad stuff that you want to get rid of.
• Vectors -- the viruses used carry good DNA into cells during gene therapy
• Stem Cells -- Cells that precurse other cells.  These cells have a high capacity for self-renewal through adult life, and can proliferate rapidly as they differentiate.
• Retroviruses --  viruses retrofitted so that they no longer cause disease, but instead can carry good DNA
• Hematopoietic -- having to do with blood, used here when referencing bone marrow transplants which replaces the body's ability to make blood
Enzyme replacement therapy- the obvious but the hardest

A Krabbe's affected infant is missing about one pinhead full of enzyme spread throughout the entire body.  It is easy to imagine swallowing a pill or injecting a tiny amount of enzyme and solving the problem.  Scientists are currently able to distill the enzyme, but two problems prevent its use.  First, delivery of such a tiny amount of enzyme spread throughout the whole body is difficult, especially to get it to cross the blood brain barrier, where it is needed most.  For example, Julia was creating GalC at 100% bloodstream levels about a month after her transplant, but it took several more months before it reached its mark in her brain, during which time the disease progressed substantially.   The second problem is much more difficult.  Unlike other enzymes GalC is very unstable.  The only solutions that can currently be used to keep GalC viable are extremely toxic to humans.  If a way can be found to keep synthesized GalC in a form that could be put into a child's body without killing the host, enzyme replacement therapy would be everyone's first choice.  Unfortunately, currently research is a long way from solving this problem.

A different twist of this theory is to reduce the amount of waste that needs to be washed away.  In the household garbage analogy, this would mean generating less trash.  Steven LeVine, Ph.D., from the University of Kansas Medical Center, has had significant results in twitcher mice by cutting down on the waste byproducts (galactosylceramide and psychosine), hence slowing the progress of the disease, with the use of L-cycloserine.  So far this is only viable in late onset Krabbe's, and only to prolong life in mouse models by about 30%, not to save it.  Furthermore, L-cycloserine has nasty side effects of its own. Unfortunately it is only viable in early onset victims if it is started at birth.  Late onset is extremely rare; Dr. LeVine quoted reports of only 50 cases thus far. Dr. LeVine listed the following factors affecting the age of onset:  1. blow to head,  2. genetic background (factors other than amount of enzyme generated),  3. mutation itself.  This treatment may be viable for broader use in transplant patients whose transplant was only partially successful, which Dr. LeVine is currently studying.

Gene Therapy - Krabbe's cure in a shot?

Theory:  Gene therapy has gained a lot of momentum in the popular press for its proposed ability to change the predestined course of certain genetic and other diseases into a disease free outcome.  The goal in Krabbe's disease is to get a copy of the GalC gene into every cell needing it in the body.  How will this work?  Gene therapy uses viruses to pierce the protective mechanisms of cell membranes.  After all, we've all been attacked by viruses, and we all know how they can affect us to make us very sick.  If the part of the gene that makes a person sick is spliced out of the virus, and a bit of DNA that cures a problem is spliced in, the good DNA can be delivered to every cell that the virus would hit if it remained a disease virus.  Very powerful viruses are being used in gene therapy research as vectors, or delivery viruses.  After the viruses have been tampered with or retro-fitted so that they no longer contain disease components they are called retroviruses.  It is good that the disease components can be removed, because some of the virus vectors being studied are cancer causing, flu causing (such as adenovirus), or aids causing such as HIV.  These viruses are used because they are so good at permeating many cells in a host.  As Dr. Sands stated, gene therapy doesn't correct the bad copies, it just adds another good copy, in this case of a working GalC gene, making 3 genes instead of the usual 2, one from dad, one from mom, and one from your friendly scientist.

Goal:  If the GalC producing DNA was spliced into a retrovirus that attacked the cells responsible for producing GalC, then all that would be necessary is to inject the Krabbe's affected child with the virus.  A simple shot or series of inoculations would cure Krabbe's!  This sure beats BMT and related complications.

How close are we?  Whereas the theory is simple, the actual undertaking is very complex.  So far researchers have made substantial progress in finding an appropriate viral vector, inserting the GalC gene, having the gene find its way into cells.  Trials on higher level animals are yet to be made.

• Mohammad Rafi, Ph.D., from Thomas Jefferson University, the same location Dr. Wenger, who diagnosed most of our children, has succeeded in placing GalC containing retroviral vectors into twitcher mice.  Twitcher mice are mice that are missing GalC, which causes them to twitch uncontrollably as they manifest the disease that is called Krabbe's in humans.
•  Miguel A. Gama Sos, Ph.D. from Mt. Sinai School of Medicine in NY has been able to reverse the Krabbe phenotype (stop the symptoms from appearing or getting worse, and possibly improve) in twitcher mice by inserting human brain cells of early neuronal lineage that secrete GalC using retroviruses.  It is noted that the mouse cells that were already affected by Krabbe's were happy to use the GalC secreted by the new cells, possibly affecting some repair.
• Krishna J. Fisher, Ph.D. from Tulane University has spliced a green fluorescent protein from a jelly fish to make an adeno-associated virus vector (rAAV).  When this virus was injected into mice, the green fluorescent protein (GFP) made their feet and other places not covered by hair glow green!   When it was injected into cat eyes, the eyes glowed green. The humor of this experiment is apparent, but the manifestations are profound.  Since the recombinant adeno-associated virus can carry the gene to glow green, the goal is to get it to carry the gene to make GalC rather than GFP, in humans rather than cats.  This will be tried on rhesus monkeys with Krabbe's disease, as soon as one is available.  It is worth noting the rAAV is a powerful virus that affects many cells in the body, but does not carry any associated disease that harms humans.  This significantly increases the safety of the virus.  Furthermore rAAV targets neurons, of particular interest to Krabbe's victims.  Unfortunately, there was some inflammation associated with these trials, a side effect which will need to be overcome before human trials.
• Mark Sands, Ph.D. from Washington University in St. Louis, has accomplished murine (mice) gene transfer using rAAV GalC, but despite being able to prove that the virus transferred the DNA, so far there has not been much clinical clinical improvement in the life span or behavior of the mice.  Interestingly, the genes have permeated much of the cerebrum ('thinking" cortex) and brain stem (controls basic functions), but have avoided the cerebellum (motor cortex) of the brain, raising the question of a possible barrier between the cerebellum and other areas of the brain.
• Paola Luzi, Ph.D., also from Thomas Jefferson University in Philadelphia, is using an SV40-based vector to deliver GalC to deficient cells both in vitro (in a test tube) and in vivo (in living creatures.  Unfortunately, Julia kept me quite busy during this presentation, and I didn't catch up with Paola later, so I am unable to report specifically how the SV40-based vector differs from the other vectors mentioned above, but promise to find out and let you know!
Ethical considerations and editorial comment:  Gene therapy is controversial because while what we Krabbe's families want is to repair a devastating genetic error, the same concept could eventually be used to insert DNA that would enhance various intelligence factors, cosmetic features, or a variety of other socially determined attributes.  This brings up questions originally pondered by eugenics aficionados.  Clearly it is right to seek therapies to save our children's lives, and although what is learned by researchers may some day be misconstrued for negative purposes, the same can be said of most new technologies.  Many of us have other children who are carriers of Krabbe's.  Gene therapy holds the best promise for an efficient cure:  a shot of GalC containing virus, and a child genetically determined to die sadly young grows to be a normal adult.

Bone Marrow Transplant - Today's only treatment

Although gene therapy is the most promising future cure for Krabbe's, the only currently available treatment is bone marrow transplant.  The earlier the treatment, the more effective, to the point that transplants done before symptom onset may even be considered a cure.  What has been learned about transplants, and what is available today?

Bone Marrow and Cord Blood Transplants
Everyone on this list is familiar with bone marrow transplant and what happened to Julia.  The theory is that the patient's old bone marrow is replaced with new marrow that doesn't have the genetic defect causing it to miss producing GalC.  It sounds easy, but the practical experience is otherwise.  The heavy chemo that kills off the marrow to begin with leaves a plethora of side effects; the new marrow may or may not engraft; the engraftment may be rejected by the body; there is a lengthy time in which the patient is immunosuppressed during which even a slight infection may be fatal; the disease progresses for six to twelve months as the GalC finds its way to the target neural cells.  Nonetheless, four Krabbe's late onset patients were successfully transplanted by Dr. Krivit at the University of Minnesota, and Dr. Kurtzberg has transplanted 13 patients at Duke, with 8 surviving.  Two others have been transplanted at other institutions, both of whom survived, one in St. Louis, the other at Columbia in NY.

One difficulty with transplants has been finding a donor.  Krabbe's kids degenerate quickly.  Only about 25% of transplant candidates have relatives whose blood factors match their own closely enough to make them donors, and after relatives, bone marrow matches take a long time to find.  Also, if the donor is a carrier, then the new marrow will only produce a reduced amount of GalC, in a person who needs some 'frontloading' of this substance.  Cord blood has solved this problem for many, including Julia.  There are now at least two large cord blood banks in this country, one in NY (from which Julia's donor came), and a new one in North Carolina.  The stem cells in cord blood are so immature that they don't need to match the recipient's HLA values as closely, yet they carry a smaller graft vs. host risk.  The down side is that the cord blood stem cell immaturity may mean that it takes longer for them to engraft and produce the wide variety of mature blood cells needed to support health.  The ease of finding a suitable stem cell donor very rapidly usually outweighs these factors.  With infantile Krabbe's there is no time to spare.  The first cord blood transplant was done in 1988 for a different disease.  That child is now an adult.  This treatment has progressed rapidly.  Dr. Kurtzberg indicated that one of the next stages is to accomplish the same thing that a full transplant currently accomplishes with a mini transplant, which causes fewer side effects.  Unfortunately this isn't yet an option, but may be in the future.  One advance in transplant technology is the size of person who can receive cord blood.  Cord blood is limited to the amount of blood that is in the umbilical cord at birth.  If the patient is very large there may not be enough stem cells in the cord blood sample to cause engraftment.  Stem cell enhancement is now available in some cases, an Ann Arbor Company, Aastrom, being a leader in that technology.

Dr. Kurtzberg made two points during her presentation that are very dear to my heart.  First, she adamantly supports newborn screening.  If we know about Krabbe's early we can treat children  before symptoms are prevalent, before they loose their ability to smile, eat, kick, focus, and more, as Julia did.  More about this below.  Second, transplant is expensive in terms of resources.  It would be better if all of the unknowns could be evaluated on animal models so that we could minimize both the suffering and expense of transplanting humans, but as the parents of Krabbe's kids know, there is no time to wait for that after a child is diagnosed.  Dr. Kurtzberg stays in this business where so many kids loose the battle because of the ones that win, what humanity learns from each success and failure, and because of how many more will be saved because of the transplants that occur today.

In Utero Transplants:
If transplanting soon after birth enhances future function, then transplanting before birth should be the holy grail.  In utero transplants have been attempted three times thus far.  The first child over-engrafted, perhaps the result of too many stem cells.  The second two children survived the transplant, only to die later, but did not engraft.  This may have been the result of too few stem cells, perhaps an over compensation of the number of cells given to the first in utero child.  Dr. Karin J. Blakemore, M.D. is optimistic that the procedure can be honed to success through trials on canine models of Krabbe's, Cairn terriers and White Highland terriers.  Interestingly, there is no ill effect on the mother from the in utero treatment.  Another side benefit of in utero transplant is that since the immune system of the fetus is so immature, it does not fight the donor cells in the same way that an older child may develop graft vs. host.  In fact, a few t-cells (immune system cells) must be transplanted to allow engraftment to occur.  Julia's transplant was t-cell depleted, which aids in cutting down graft vs. host disease.

Animal models
Bone marrow transplants on twitcher mice have been in the literature for a long time.  More research continues.  David Archer, Ph.D. from Emory University is working on in utero transplants in twitcher mice with significant success.  He has had engraftment, reduction in psychosine (the bad waste product), and extension of life to about three times the normal expectancy for a twitcher mouse.  At about 100 days, however, these mice die despite previous improvement.  Nonetheless, this research is very promising for a wide variety of diseases, including sickle cell anemia and thalassemia, as well as other lysosomal storage disorders including Krabbe's.

Neural Stem Cell Transplant

So what's next?  From the standpoint of the parent of a child who produces full levels of GalC and is from that standpoint "cured" of Krabbe's, neural stem cell transplant research is very exciting, and combined with other treatments above could mean not only high cure rates, but high function for this disease in the future.  One of the researchers even suggested that in the future a bone marrow transplant will be accompanied by a neural stem cell transplant.

Ian Duncan, Ph.D. from the University of Wisconsin reminds us that there are two ways to remyelinate:

1. 1.    Endogenous repair
2. 2.    Stem cell transplant
Some endogenous repair occurs on its own. We all learned as kids in biology class that once you killed a brain cell (however you accomplished this feat ;-) it was gone forever.  We now know that this is not wholly true. In fact, children like Julia and others have proven this.  She is better, she breathes on her own, she smiles, she eats, and so on.  Another study was recently published in which stroke victims with no use of certain limbs were able to regain use if given appropriate stimuli.  Nonetheless, when massive diminution of neural tissue has occurred, endogenous repair is not usually enough to obtain full function.  Neural stem cell transplant may soon be the answer.

The cells that grow myelin are oligodendricyte glial cells.  These are mature cells, that do not change into other types of cells, or readily replicate upon demand.  Stem cells are theoretical cells that come before all other cells, like an embryo that divides and divides and eventually differentiates into the cells that comprise a person.  Neural stem cells have the potential to generate into brand new oligodendricytes, as well as other necessary neural cells of different denominations.  These neural stem cells can be isolated and grown in a test tube.  Barbara Tate, Ph.D., from Children's Hospital of Boston, presented evidence that murine neurons will engraft, myelinate, differentiate, and even continue to survive in Shiver mice who have had nothing else done to stop the progression of their disease!  The host cells do not produce myelin, only the donor cells.  Most interestingly, the stem cells seem to track to injury areas, especially the oligodendricytes.  How they know where to track, or what signal is sent out by the damaged area, is a mystery.  Ian Duncan impressed on a number of scientists that injection of the stem cells into the ventricles has given good results.  I impressed on him that Julia already has a shunt heading directly to her ventricles...

Every gene has the information to produce a single protein.  Myelin basic protein is made where the myelin sheath is put together.  Robert M. Gould, Ph.D. from the NY State Institute for Basic Research, is working hard to identify which genes are important for myelination.  Once GalC is present, especially if damage has already occurred, the child is on a hurry up mission to create new myelin and new neural pathways as fast as possible while the period of brain plasticity is still viable.  In other words, if we can enhance myelin growth by giving the myelin genes/proteins a little push, we can enhance myelin growth during the time when a child is open to learn.  This research is still a long way from practical fruition, but from Julia's standpoint, some of the most important.

Ethical considerations:  Research on stem cell implantation has moved to the human level.  Stem cells from fetuses have been implanted into the brains of Parkinson's patients, causing relief of their disease.   Many disagree with this type of research and its implications.  The good news is that fetal cell implantation will be ancient history soon.  Stem cells from other non controversial sources can be grown in test tubes.  These are the cells that will be used.

Ancillary Research

Rhesus Monkeys with Krabbe's discovered

There are many avenues for research, but much of it is not ready for human experimentation.  It is very important that many of these therapies be honed in animals before they are tried in humans.  Twitcher mice and several breeds of dogs provide functional models of mammals missing the same enzyme as Krabbe's kids, but the animals are themselves so different from humans that it is sometimes difficult to extrapolate what a human outcome would be.  Fortunately, a Krabbe's rhesus monkey was discovered in a primate farm at Tulane University in 1987, as presented by Marion S. Ratterree, DMV.  Rhesus monkeys do not regenerate very quickly, so only a total of 5 Krabbe's rhesus monkeys have been conceived since the discovery, and only the current monkey has survived to be available for study.  Her name is Daisy Mae, she is 3 months old, and in the end stages of the disease.  The video we saw of her amply demonstrated her disability, especially as juxtaposed against the control monkey, Leroy Brown, a mischievous little guy born the same day.  Daisy Mae has been used for data gathering, but no treatment has been presented.  Many of the parents at the seminar thought that all future Krabbe's monkeys born, especially considering what a rare event that is, should have a variety of treatments ready to see what can be done to alleviate their symptoms and prolong life.

Newborn Screening program being developed in Australia

If we can determine at birth who has Krabbe's, we can treat the child before symptoms develop, giving a high probability for total cure.  Phillip Whitfield, Ph.D. from the Women's and Children's Hospital in Adelaide, S. Australia is developing a test that will use tandem mass spectroscopy to screen for a variety of lysosomal storage disorders, including Krabbe's.  There is a primary storage glycolipid in the blood of Krabbe's victims, causing a secondary accumulation of certain oligosaccharides.  The test will look for this oligosaccharide, and a whole spectrum of other diseases, the combined prevalence being just below cystic fibrosis.  This kind of prevalence makes testing millions of people cost feasible, whereas testing for only one disease that pops up in 1/250,000 people not worth the cost and risk.

A tiny amount of blood will be taken from the child, as is currently done in this country in PKU testing.  This will be spread on a small card, sent to a lab, and put through a computer to be read like key punch cards were a couple of decades ago.  Dr. Whitfield asked for help in obtaining samples from Krabbe's patients, since there are only a couple of cases diagnosed in Australia each year with Krabbe's.

Dr. Whitfield hopes to begin testing this screening program in Adelaide within the year, in all of Australia after that.  Then it will be up to us to convince legislators in this country that the benefits of screening outweigh the cost.  We will watch Dr. Whitfield's trials with great interest, and gear up to spread the message when the test is ready to be used for large scale screening.

Seizures

Patricia Duffner, M.D. gave an overview of the variety of seizures in children, with a brief discussion of treatment options.  It is interesting that seizures are convulsions stemming form neurons, not myelin, since we in the Krabbe's business focus so often on myelin.  Many seizures are not dangerous, but some are, and it is important to seek treatment if seizure like activity is suspected.

Other Topics

Krabbe Registry and Proposed Research Library

All of us were asked to fill out and return to Hunter's Hope a survey prior to attending the symposium.  This data is being collated by Dr. Laurene Tumiel and Karen Crooks, M.S., at the State University of New York at Buffalo.  Here are a few of the results compiled of the respondents so far:

• mean birthweight - 7.4 lbs
• mean birth length - 20.3 inches
• mean age at diagnosis - 13 months
• median age at diagnosis - 6 months
• range of age at diagnosis - 1 month - 12 years
• 86% of the kids smiled before diagnosis, only 29% after diagnosis
• 21% had a kidcart at the time the parents responded
• 16% had a stander
• 73% of the kids had seizures after diagnosis
• 50% lost their sight after diagnosis
• 47% received a g-tube
• 57% were on seizure medication after diagnosis
• 40% were on reflux medication after diagnosis
• 71% received PT, 43% received OT, 51% received Massage Therapy, 36 received PPD
• each child averaged 2 siblings with a range of 0 - 5
This group is considering compiling a library of Krabbe's research and related articles.

Health Care financing

Donna Andrzejewski, the mother of a child who has a different, rare, and very invasive medical condition talked about her experience as a member advocate for S.K.I.P., Sick Kids need Involved People, an independent nonprofit organization offering case management and advocacy to NY residents.  She offered valuable tips for navigating you way through insurance company, social security, and medicaid waiver bureaucracies.  Advice included, *read your policies thoroughly, *keep up on new insurance judgments and rulings, *when told no make sure to get the reason in writing, *always be polite, but firm.

Fundraising and Volunteerism

Hunter's Hope Vice-President & Chair, Jacque Waggoner discussed the ongoing candle campaign, proposed new bear style for next year, and goals to enhance fundraising in the future so that funding can continue for all of the research above.  Building awareness is key.  Hunter's Hope will continue to support groups and families in the field who hold events or garner publicity through collateral materials such as the candles and CD's, updates about publicity generated by the Kelly's, and public events.  The new website should be running soon.

One of the goals of Hunter's Hope is developing awareness of the disease and its initial presentation among pediatricians.  Several methods of doing this were discussed.  Information off the registry may be helpful.  For example, if the first sign of the disease is frequently retracted thumbs, it would be worth making sure that if constant retraction of thumbs is noted in an infant, further testing is necessary immediately.

Advocacy

Dr. Mark Sands pointed out that parents make a powerful legislative lobby.  He has received calls from legislators who have been hassled by parents to fund various research projects.  The congressmen wanted to know how prevalent the disease was, and how many people a cure would affect.  Our disease is small, but the manifestations of finding treatments, screening mechanisms, and cures affect many other diseases.   By carefully formulating letters and targeting legislators, we can help be sure that some of the massive National Institute of Health budget is spent on Lysosomal Storage Disorders, of which the leukodystrophies are a subset.  All of the research on Krabbe's benefits the other 40 diseases in this group.  The total group of lysosomal storage disorders affects nearly as many people as cystic fibrosis, for example, which has a powerful advocacy group.  A committee of people was formed to compose template letters, and news about where to send them will be published on the Hunter's Hope website.

Equipment Exchange

LeA Gartzke's mom, Micki, is putting together an equipment exchange program so that expensive equipment can be passed on to other children once it is no longer needed.

In closing I want to congratulate all of you readers who plowed through this entire email and made it to this point.  You win the million!  Now that I have your attention, that's the million thanks for being supportive of Julia during the last couple of years.  We are now on a mission to build function, so those famous well wishes and prayers that so often carried us through critical periods in the past are still much needed.  Today, I especially want to thank Jim and Jill Kelly for pursuing the Hunter's Hope dream, because it takes a recognizable name to raise substantial funds for diseases.  Liz Taylor does it for AIDS, Michael J. Fox is doing it for Parkinson's, Christopher Reeves for spinal cord injuries, and so on.  Jim and Jill could have crawled behind a wall of privacy, but instead they spend much of their free time promoting Hunter's Hope.  The results were obvious this weekend.  Thank you from everyone who has suffered at the hand of this disease.  So much has happened since the symposium last year, I can hardly wait to see how much more progress is made by the time next year's symposium rolls around.

~Wendy, Julia's mom 

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