What exactly is Niemann Pick Type C?
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 22 minutes, a child is born with a LSD.  Addi and Cassi have a rare LSD and one that is fatal.

In Addi and Cassi’s case, they were born with a cholesterol metabolism disorder where harmful amounts of gangliosides, a very complex type of lipid, collects in their cells (not blood) and clogs them up so they don’t function properly.  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 (and as we understand Parkinson’s disease).

What are the first symptoms of Niemann Pick Type C?
Symptoms vary from person to person.  We keep hearing common threads when we talk to parents: jaundice at birth, enlarged liver and/or enlarged spleen.  The organ enlargement is often prolonged and unexplainable.  If your child expereinces these symptoms, NPC should be ruled out.  Also, if your child has trouble with balance and coordination in combination with these other symptoms, this could also be an early sign of NPC.

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 and NPC (we just ask that you not bring this up if we’re with the girls).  We are not in crying mode, we are in action mode and have made great strides in a short period of time.  In our minds, helplessness equals hopelessness.  We are determined to find therapies for NPC.   With your help and support, we can beat "Childhood Alzheimer’s."

How did Addi and Cassi get Niemann Pick Type C?
Genes are found in pairs within the body.  When a child is conceived each parent passes one gene from every pair of genes to their child.   Although molecular analysis is still being conducted (DNA mapping), we believe that Addi and Cassi inherited two affected NP-C genes at conception (in rare cases there is only one gene causing the problem).  For a simple and informative overview of how we all inherit our genes, visit 23andme.com. 

 

 

 

 

 

 

 

 

 

 

 

 

How did Mom and Dad end up with faulty NP-C genes?
Just like Addi and Cassi, we inherited the affected genes from our ancestors on both sides of our family.  Genes are simply passed down from one generation to the next.   We both carry one good copy of the NP-C gene and one affected copy of the NP-C gene.  Since we only have one affected gene and are simply "carriers," we do not exhibit the disease.

Did you know you were carriers of a defective NP-C gene?
We had no idea we were both carriers of a faulty NPC gene as there is no genetic or prenatal testing to detect it.  Statistics show there is a 25% chance for a child to inherit two affected genes if both parents are carriers of that defective gene.

Are there any medications available to treat Addi and Cassi?
There is one drug called Zavesca (Migulstat) that is in the second phase of a clinical trial and is the only drug currently recognized to "possibly" provide benefits to NP-C patients.    It costs $160,000 a year to have Addi and Cassi on this drug.  Zavesca is used to treat Gaucher’s disease but was approved by our insurance company “off label” to treat the girls.  Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug’s originally approved label. 

How do you get the drug Zavesca?
Blue Cross approved Addi and Cassi for off label use of Zavesca and they have been a wonderful insurance company throughout this process.   We actually receive the drug through the mail from Curascript, as they are the only provider of the drug in United States.  There are a number of new compounds currently being researched by scientists and we are aggressively pursuing all types of experimental treatment options in parallel to taking Zavesca.

How are Addi and Cassi doing currently?
The girls are doing quite well and are in the very early stages of the disease. They have enlarged spleens and mildly enlarged livers which are not causing many issues at the moment.  They are having very slight neurological symptoms and are having some difficulty with gross and fine motor skills. 

For example, they walk and run but it is difficult for them to jump or navigate stairs on their own.  Generally, they appear to be quite normal 4 year old girls.  They talk, they laugh, they interact and like to play hide-and-seek, they love cartoons, they love to color and to look at picture books.  They like to play with other kids and most of all are very loving and affectionate little girls.  We are incredibly blessed to have them in our lives.

Do Addi and Cassi know they have NPC?
No.  The girls are still too little to know what a disease is and we are working on keeping things as normal as possible for them for as long as possible.

What is the progression of the disease?  Does NPC move slowly in some and more rapidly in others?
The disease acts differently in all people and doctors are unable at this time to give us any indication of how fast NP-C will progress in Addi and Cassi’s bodies.  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 cases of adult onset.  NPC is most commonly a childhood illness.

Will Addi and Cassi die from NPC?
The disease is fatal.  We are doing everything in our power as parents to not let this happen to our beautiful daughters.   We are being extremely aggressive and creative in terms of coming up with a plan to try and stop the disease and are looking into additional experimental therapy options beyond Zavesca.   We need donations to help us speed up finding therapies and ultimately a cure.

Can diet help with Niemann Pick Type C?
Diet is not considered impactful in the management of the condition but we are trying a zero cholesterol diet at the current time as we have seen some improvements since eliminating cholesterol from Addi and Cassi’s diet. 
We have learned that there are different kinds of cholesterol in our bodies.  There is the kind of cholesterol our bodies make naturally and the kind we eat when ingesting foods.  The fact is people don’t need to ingest any cholesterol because we all make enough cholesterol naturally to survive.  Addi and Cassi’s condition is thought to be solely influenced by the kind of cholesterol their bodies make naturally.  For some reason the natural cholesterol  they produce stays trapped inside their cells.  Cholesterol starts to accumulate and slows down cells leading to cell death.  Think of a cellular traffic jam.   As this process 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, NP-C is often overlooked by doctors and children with the disease can often go undiagnosed for many years.   It took close to two years for us to receive a diagnosis of NP-C.  

When Addi and Cassi turned 2 years old, 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 liitle cause for concern.  Over the next year and a half, we took Addi and Cassi to Stanford multiple times and they 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 to get extremely worried.  We decided to seek a second opinion.   More tests were conducted by Children’s Oakland Hospital.   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 but ruled out.  We started to notice that Addi and Cassi were having problems with their balance and has 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 NP-C.

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 NP-C?
Testing for NP-C is extremely complicated.  It’s overwhelming when you’re told that your children could have a fatal and devastating disease such as NP-C and that you will have to wait months for an answer.   We know of a family in Oregon who have two children, ages 10 and 7, who they believe have NP-C.  The parents were told it will take 3 months for an answer from DNA testing.  We embarked on a different path for an answer.

Based on a recommendation by Dr. Patterson at Mayo Clinic, we were able to get a preliminary diagnosis in 10 days based on a specific kind of test conducted by electron microscopy.  Since NP-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 NP-C.

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).  Basically, they watch the skin sample grow in a dish and see what happens with cholesterol.  It can take many weeks for a cultured fibroblast result and sometimes the skin samples do not grow requiring the testing to be redone.   Apparently another way to test for NP-C 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 NP-C 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 the girls 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 a pre-school program.

Are Addi and Cassi in regular school?
Yes.  Addi and Cassi attend Pleasant Valley Elementary, a local elementary school and that has special 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.

How are you coping?
We remain very optimistic that we can find therapies and ultimately a cure for NP-C.  However, we must accelerate research quickly for all NPC kids and we need your help.