Frequently asked Questions about NPC

I came across this blog that Hugh Hempel, Addi and Cassi's Daddy, posted. Of course I know the questions and answer because we live it everyday but for most of you it is still a disease with so few faces. It is still hard for most to understand and therefore it is difficult to spread the word about a disease you don't really know about except that Tylor has it and it is fatal.

I really felt it was important to share his post with you and I hope you will pass it along. Also a great idea would be to print it out so you have the information handy if anyone asked you about NPC.

The video above is done by the Hadley family. This video is very powerful! It explains about NPC and how they family is coping with this disease.

Thank you Hadley's and Hugh for sharing your stories!!

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.

The 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.

Common Questions taken from addiandcassi.com