First Lupas, then MS, then Cancer. Just Kidding – You Have Adult NPC!

February 8, 2008 by Chris Hempel
Filed under NPC Family Stories

Sweet Gabrielle LaVerde

January 7, 2008 by Chris Hempel
Filed under NPC Family Stories

An email popped into my inbox from my new friend, Danielle LaVerde, who has a sweet little girl named Gabrielle who has Niemann Pick Type C like Addi and Cassi. Danielle lives in Florida and like me she is doing everything possible to save Gabrielle from this horrible disease. Her letter makes me cry and cry and cry. Someone else is going through the same nightmare. I am putting together a donations package so we can raise money for Niemann Pick Type C research and I am asking scientists, researchers and parents of NPC children for submissions to help us raise awareness and money. Danielle submitted Gabrielle’s story and I ask that you to take a moment out of your busy day to read it. If you have not made a donation, please consider making one for our children. Even the smallest amount helps. And please help us get the word out about our kids. We are Mom’s on a Mission – curing Niemann Pick Type C!

My Dreams For My Daughter Gabrielle

All I ever wanted to be was a Mom. From an early age, I knew that was what I wanted to be when I grew up. On career days at school, while my friends aspired to be teachers, nurses, lawyers, and even astronauts, I wanted to have children and stay at home to raise them – – four of them to be exact. My goal was to raise, kind, secure, loving children. I wanted to know them and I wanted them to know me. I wanted to talk with them and watch them play baseball and dance. I wanted to laugh with them, read to them, dance with them, and have dinner each night while hearing about their day at school.

Motherhood did not come easy, though. After over five and a half years of trying to conceive, including a positive pregnancy test discovered to be false the day after my husband’s father suddenly died, medication, surgery, and swallowing 40 herbs a day, I finally found myself pregnant. My husband and I were in complete disbelief. We were overjoyed that we would finally have the child that we’d waited so long for. We had already loved this child for years and now she was real. We thought we had survived the most horrible event of our lives.

After a relatively uneventful pregnancy and delivery, we had our precious baby – Gabrielle. We gave her that name because she was our beloved angel, new and fresh from God’s very hands. She was a miracle, prayed into existence. She was a tiny little thing, only 5 pounds, 15 ounces and 19 inches long. The first eighteen months or so of her life were wonderful. She was a happy, sweet, smiling little girl, with big, sparkling eyes and she had the best belly laugh we’d ever heard. She was everything we’d ever dreamed of and more. She developed normally and hit her milestones on time, including her first words. She pointed at everything asking, “Watsat?” “Watsat?” She started walking later than most, but was toddling around by 15 months, well within the standard time frame.

Somewhere around 18 months we began to notice that she was not quite keeping up with other kids her age. They were picking up new words, she was not. They were growing more stable on their feet, she was not. By the time her second birthday rolled around, we knew something was wrong. Her pediatrician, however, thought she was “perfect” and that she would “catch up” by the time she turned three.

By her third birthday, it was even clearer to us that she was having difficulty with her speech and gait. It was obvious that her balance and coordination were not what they should be. Finally receiving a referral from her pediatrician, we took her for a complete evaluation. Her fine and gross motor skills, as well as her speech, sight, and hearing were all tested and it was determined that she was “developmentally delayed”. Mild Cerebral Palsy was even mentioned as a possibility. The recommendation was that she begin classes as well as speech, physical, and occupational therapy at the local elementary school.

Months went by and it was apparent to us that while she greatly enjoyed school, the classes and many therapies were not helping her progress. By her fourth birthday, we were very frustrated with her pediatrician. It was plain that Gabrielle was having a medical problem and that her doctor was not going to help us determine what was wrong. She must have felt we were being obsessive, over-protective, first time parents making something out of nothing. Her four year check up with a new pediatrician brought us new information and new hope for an answer. She told us several things about Gabrielle that her previous doctor had never shared with us. For instance, that she has connective tissue issues – – hyperflexible hip joints and nearly flat feet. The doctor did not have any idea what was wrong, but agreed that it was unmistakable she had a medical problem and recommended that we immediately schedule appointments with a Behavioral Pediatrician, a Geneticist, and a Neurologist to aid with diagnosis.

The Behavioral Pediatrician worked with us for about one year, offering helpful suggestions and testing her for conditions she knew Gabrielle didn’t have simply to rule them out, such as Autism. In the meantime, we also worked with a Geneticist and a Neurologist. For two years, Gabrielle was subjected to countless blood tests. I used to count how many vials of blood were taken from her, but stopped around 50. Holding down my terrified, screaming child along with 4-5 other people so a nurse could draw blood was one of the hardest things I’ve ever had to do. I would beg God to make it stop; crying as hard as she was by the time it was over. She also endured EEG’s, MRI’s and CT scans. All tests returned normal with the exception of the EEG’s which showed that she was having absence seizures while she slept. Four attempts at different seizure medications failed. One in particular had horrible side effects – – by the third day on the medication, she could no longer put a fork to her mouth and by the fourth day, she could not sit up. All medications were stopped as her doctor felt her system was just too sensitive to tolerate any anti-seizure medication.

We had consulted with literally the best doctors in Orlando, yet no one knew what was wrong. We took her to Jacksonville to meet with a Neuro-Muscularist as her Geneticist was convinced she had a mitochondrial disorder. After waiting weeks to see him and spending four hours at his office, we left with another list of tests. With four more months of testing under out belts, we returned to the Neuro-Muscularist with results in hand – – all negative. The doctor’s response was that he was very glad to see she didn’t have any of those conditions … and that he would see us in a year. We were astonished and shocked that he could offer us nothing else. After pressing him for help, he finally offered that if she were his child, he would take her to the Kennedy-Krieger Institute at Johns Hopkins.

Developmentally, Gabrielle was continuing to decline. Walking, coloring, running, playing, skipping, riding a bike, and jumping were impossibilities for her. Emotionally she became increasingly frustrated, shaking her fists and gritting her teeth while growling in protest at her own body. She knew what she wanted and she knew her body would not cooperate with her mind to achieve it. She understood everything that was said to her, responding appropriately if asked to choose between two items or pick something up, and laughing at what she thought was funny. There were times she would sit next to us on the couch and open her mouth to speak; only nothing would come out. She’d try and try, but simply could not talk. It was heartbreaking. My husband and I cried so many tears. The pain and heartache of doing everything you can think of to help your child and come away without an answer or any improvement was more than we could bear.

We felt helpless as we watched our beloved little angel fall further behind and loose the few skills she did have. She used to count to 13. She used to fill in the next letter when singing her a-b-c’s, and the next word when reading familiar books. She had looked at everything with a sparkle in her eyes. She always appeared to be pondering something very important … the wheels in her head were always turning. As my friends talked, as all parents do, about how well their kids were doing, learning new things on a daily basis and relaying funny stories about things their kids said and did, my precious child was slipping further and further away. And nothing we did seemed to make any difference.

We applied to and were accepted by Kennedy-Krieger Institute. By then, Gabrielle had stopped talking entirely and all we had was a 3-inch thick notebook full of test results that told us every illness, ailment, syndrome, disorder, and disease she didn’t have. Not knowing whether to have her seen by the Movement Disorders Department or the Neurology Department, they scheduled her with both. We went to Baltimore in early 2007. By now, she was 5 years old and we were no further ahead than when we’d begun. Once again we left with a list of suggested tests – – and a warning that it was their opinion that she had a progressive, degenerative disease. Devastation does not begin to touch how we felt. It was huge blow that we were not prepared for. We tried to convince ourselves that they were wrong. This could not happen to our precious girl. After all we went through simply to have her, this could not be her fate. It just wouldn’t be fair.

After a few more tests, and a consultation with another specialist in Brandon, Florida, we moved forward with the skin biopsy necessary to determine whether or not she indeed had Niemann-Pick. The six week wait was relatively painless. Two of her doctors (including the ordering Geneticist) assured us that this was just another test they were performing in order to rule out yet another disease. No one seemed to think this test was going to be any different than all the others. But this one was. This was the answer we’d been searching four years to find … but this was not the answer anyone would ever want. Our daughter’s answer was a death sentence.

Heart-shattering, soul-crushing pain was all we knew at that point. We felt completely helpless. I found myself begging God to take her quickly. I couldn’t stand the thought of watching her slowly disappear … watching her suffer … watching as she looked to me for relief and being powerless to give it to her … watching her endure the end of her life before she had any real chance to live. My dreams of happiness for her were gone. Her whole life she would only know frustration, disappointment, grief, pain, and despair.

Hope was nowhere in sight. We were destroyed. But my friends, family, and coworkers offered a sliver of hope when they ran to my side. They cried with me, held my hand, and let me borrow their strength. They promised to stay with me through whatever came our way. Gabrielle’s doctor offered us another sliver of hope when he suggested several treatment options. So we decided to fight with all we have. We had been fighting for her all her life and we were not about to stop.

My dreams for my daughter have changed. Now my dream is that she will be able to tell us her wants … what she needs … what she feels. My dream is that she will be able to walk wherever she wants without help. My dream is that she will be able to ride a bike. My dream is that she will not die.

The four children I wanted will never happen. I feel I don’t get the choice of whether or not to have more children. I could never take the chance of giving this disease to another child. All I have is my sweet Gabrielle, who still has big, sparkling eyes and the best belly laugh I’ve ever heard.

Tags: Deltona Florida, Gabrielle LaVerde, Kennedy Krieger Institute, Moms On A Mission, Niemann Pick Type C

The Puzzle That Desperately Needs To Be Put Together

January 2, 2008 by Chris Hempel
Filed under NPC Family Stories

Common Questions About Niemann Pick Type C

December 1, 2007 by Daddy
Filed under About Niemann Pick Type C

9 Comments

This video was made by our good friends, The Hadley’s, who also have two children with Niemann Pick Type C disease. This video is easy to understand and gives an overview of Niemann Pick Type C disease and how we are working together to find treatments and a cure.

FREQUENTLY ASKED QUESTIONS

What is Niemann Pick Type C disease?
Niemann Pick Type C is a lysosomal storage disease (LSD) which is a genetic disorder caused by abnormalities in genes or chromosomes. There are group of over 50 lysosomal storage diseases that result from problems in lysosomal function. Every 30 minutes, a child is born with a LSD.

Addi and Cassi were born with two genetic defects on Chromosome 18 on the Niemann Pick Type C gene. Everyone in the world is born with the Niemann Pick Type C gene and could not survive without it. The gene regulates cholesterol metabolism in the human body and there are approximately 500 cases in the world.

In Addi and Cassi’s case, their double genetic defect causes harmful amounts of gangliosides, a very complex type of lipid, to collect in their cells (not blood) and clog them up. The cholesterol accumulation leads to cell death. As cells die, this causes neurological deterioration and also problems with the liver and spleen.

Impaired ganglioside metabolism may also be highly relevant to Alzheimer’s disease. In fact, Niemann Pick Type C is often referred to as the “Childhood Alzheimer’s.”

What are the first symptoms of Niemann Pick Type C disease?
Symptoms vary from person to person. We hear common threads when we talk to parents: jaundice at birth, enlarged liver and/or enlarged spleen, ataxia, cataplexy, and seizures. Organ enlargement is often prolonged and unexplainable. If a child has trouble with balance and coordination in combination with these other symptoms, this could also be an early sign of Niemann Pick Type C. Wikipedia has a complete outline of NPC symptoms.

How did Addi and Cassi get Niemann Pick Type C disease?
Genes are found in 23 pairs within the human body. When a child is conceived each parent passes one gene from every pair of genes to their child. Addi and Cassi inherited two affected Niemann Pick Type C genes at conception. For a simple and informative overview of how we inherit our genes, visit Pathway or 23andme.com

How did Mom and Dad end up with faulty Niemann Pick Type C genes?
Just like Addi and Cassi, we inherited the affected genes from our parents on both sides of our family. Genes are passed down from one generation to the next. We both carry one good copy of the Niemann Pick Type C gene and one bad copy of the Niemann Pick Type C gene. Since we only have one affected gene we are simply considered “carriers,” and we do not exhibit the disease. However, it is unclear if carriership of a faulty NPC gene could impact our health over the long term.

Did you know you were carriers of a defective Niemann Pick Type C genes before you conceived?
No. We had no idea we were both carriers of a faulty NPC gene. Their was no genetic or prenatal testing to detect it. A few new genetic testing companies are now testing parents for rare genetic defects such as Counsyl, 23andme.com and Pathway Genomics.

Are there medications available to treat Addi and Cassi?
There is one drug called Zavesca (Migulstat) that is in the second phase of a clinical trial. Zavesca is the only drug currently recognized to “possibly” provide benefits to Niemann Pick Type C patients. The drug has been approved in the European Union but not yet the United States. Zavesca is used to treat Gaucher’s disease and was approved by our insurance company “off label” to treat Addi and Cassi. Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug’s originally approved label. It costs approximately $160,000 a year to have Addi and Cassi on Zavesca.

In April 2009, the U.S. Food and Drug Administration (FDA) granted special permission under its “compassionate use” program for Addi and Cassi to receive intravenous infusions of 2-hydroxypropyl-β-cyclodextrin, a non toxic sugar compound. Addi and Cassi are the first children in the United States to receive experimental treatment with this compound and are currently undergoing treatment at Renown Regional Medical Center in Reno, Nevada.

How do you get the drug Zavesca?
Blue Cross approved Addi and Cassi for off label use of Zavesca. Insurance companies make the decisions to provide this drug on a case by case basis. We receive Zavesca each month through the mail from Curascript, the only provider of the drug in United States.

How do you get Cyclodextrin?
Cyclodextrin is not a controlled substance and it can be obtained. We have created and submitted a special treatment protocol to the FDA in order to give Addi and Cassi cyclodextrin treatments in a hospital setting. A company called CTD, Inc. in Florida is a supplier of various cyclodextrins in the United States.

How is Addi and Cassi current health?
The girls are “hanging in there” as we like to say. They currently have enlarged spleens and mildly enlarged livers which are not causing many issues at the moment. They exhibit a number neurological symptoms and are having difficulty with gross and fine motor skills. Their ability to speak has been lost but they are still walking and recognize us. They are very loving and affectionate little girls and we are incredibly blessed to have them in our lives.

Do Addi and Cassi know they have Niemann Pick Type C?
No. Addi and Cassi do not understand they are sick and we are working on keeping our lives as normal as possible for as long as possible.

What is the progression of the disease? Does NPC move slowly in some and more rapidly in others?
Niemann Pick Type C disease acts differently in all people and doctors are unable at this time to give us any indication of how fast the disease will progress in Addi and Cassi. People who have the disease have different symptoms and rates of progression, even kids in the same family with the same genetic mutations. Addi and Cassi have early onset childhood symptoms — there are also a few cases of adult onset. NPC is most commonly a childhood illness.

Will Addi and Cassi die from NPC?
Niemann Pick Type C disease is fatal. We are doing everything in our power as parents to not let this happen to our beautiful twins. We are extremely aggressive in treating our children and have designed a strategic plan to try and stop this cholesterol disease from causing more damage. We are looking into additional experimental therapy options beyond Zavesca and Cyclodextrin.

Will diet help control Niemann Pick Type C disease?
Doctors say that diet is not considered impactful in the management of the condition but we are trying an extremely low cholesterol diet. We believe that diet does play some role in this condition. Our bodies naturally make cholesterol. The fact is people don’t need to ingest cholesterol because we all make enough cholesterol naturally to survive.

Addi and Cassi’s condition is thought to be influenced by the kind of cholesterol their bodies make naturally. For some reason the natural cholesterol they produce stays trapped inside their cells. Cholesterol accumulates and slows down cells leading to cell death. The best way to think of this is to imagine a cellular traffic jam. As this traffic jam of cholesterol occurs inside the body, it starts to cause a variety of debilitating neurological and physical problems.

How did Addi and Cassi receive their NPC diagnosis?
As we have come to find out, Niemann Pick Type C is often overlooked by doctors and children with the disease can often go undiagnosed for years. It took us close to two years to receive a diagnosis of NPC.

When Addi and Cassi turned two, they contracted a severe case of infectious mononucleosis. During an abdominal exam by our local pediatrician, she noticed that Addi and Cassi had enlarged spleens. Spleen enlargement is a common side effect of mononucleosis and at the time there was very little cause for concern. Over the next year and a half, we took Addi and Cassi to Stanford multiple times. Stanford ran a series of tests ranging from genetic testing (including Niemann Pick A and B), hematology tests and immune system deficiency tests. Nothing unusual showed up in Addi and Cassi’s blood or urine and their spleens were functioning well despite the enlargement.

When Addi and Cassi’s spleens remained enlarged for a prolonged period of time, we started getting extremely worried. We decided to seek a second opinion. More tests were conducted by Children’s Hospital Oakland. A volumetric CT scan was conducted which showed slight liver enlargement in addition to spleen enlargement in both girls. A whole series of serious lysosomal storage disorders were then tested for and ruled out.

We started noticing that Addi and Cassi were having problems with their balance and issues of “spaciness” after ingesting foods. We insisted on more genetic testing. At that time, we were told by Stanford that Addi and Cassi could possibly have Niemann Pick Type C disease.

We recommend that if your child has an enlarged spleen, they should be tested for storage disorders, including Niemann Pick Type C.

How do they test for NPC?
Testing for Niemann Pick Type C is extremely complicated. In some cases, it can take up to 3 months for an answer from DNA and molecular testing. We embarked on a different path for an answer.

Based on a recommendation by Dr. Patterson at Mayo Clinic, we were able to receive a preliminary diagnosis in10 days based on a specific kind of test conducted by electron microscopy. Since Niemann Pick Type C can’t be detected in the blood, Addi and Cassi had small skin biopsies taken from the back of their arms. We had two samples taken from each and they received a small “kitty whisker,” or stitch on their arms.

One biopsy was placed in a glutaraldehyde solution for the examination by electron microscopy which was done by Stanford’s neuropathology department. This particular test looks for intracellular inclusions (or polymorphous cytoplasmic bodies) and this test came back positive which gave us the early indication of NPC.

Th second skin biospy was sent in sterile water for a cultured fibroblast study. This is cholesterol trafficking test (measuring cholesterol esterification) and free cholesterol accumulation (by filipin staining). Researchers watch the skin sample grow in a dish and see what happens with cholesterol. It can take many weeks for a cultured fibroblast result. Sometimes the skin samples do not grow requiring the testing to be redone. Another way to test for NPC is through a bone marrow aspirate to evaluate for inclusions, storage cells and sky blue histiocytes (we never had to do this).

Final determination of NPC must be made by molecular analysis (DNA testing). Because two distinct genes can cause the disease, and more than 250 mutations have been described, molecular analysis can be time consuming and can take many months as well.

What types of special therapy will Addi and Cassi need?
We will be placing Addi and Cassi in speech, physical, occupational and vision therapy (if we can find this service locally). We are currently working to add in these types of services to our daily routine in addition to their special needs school program.

Are Addi and Cassi in regular school?
Yes. Addi and Cassi attend Brown Elementary, a local elementary school and that has special needs programs. We have no idea what to expect with school or how certain medications will react in their systems. We will need to make decisions on their schooling over time. Our ultimate goal is to make life as normal as possible for Addi and Cassi.

What should I say when I see you? Do you want to talk about this?
Don’t be afraid to approach us to talk about the girls. We are not in crying mode, we are in action mode. We have made great strides over the past two years and hope is increasing everyday.

How are you coping?
As well as can be expected. We remain optimistic that we can find therapies for Niemann Pick Type C and 100% of our focus is on this goal.

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