Brisan and Parker Stults | Living with Niemann-Pick Type C

What is Niemann-Pick Type C Disease?

Niemann-Pick Type C Disease (NP-C) is a genetic pediatric neurodegenerative disorder causing progressive deterioration of the nervous system. It usually starts to affect children of school age (4-7 years old) by interfering with their ability to metabolize cholesterol within the cell. Consequently, large amounts of cholesterol accumulate within the liver, spleen, and brain. This metabolic disorder leads to a series of neurological problems that are ultimately FATAL. NP-C is estimated to be 1 in 150,000 people worldwide, with only a couple hundred cases diagnosed in the world!  There are two genes NPC1 & NPC2 located on Chromosome 18. NPC1 gene is responsible for 95% of all the diagnosed cases with Niemann-Pick Type C. They have found over 250 mutations. Brisan and Parker have the NPC1 gene. NP-C is considered a Lysosomal Storage Disorder (Gaucher's Disease is the most prevalent.)

Life Expectancy with Niemann Pick Type C Disease

Life Expectancy with Niemann Pick Type C is younger than 20 years of age. However, there is no normal to go from. Additional information puts this disease into perspective according to the American Journal of Medical Genetics Part A. “The average age of diagnosis for NPC1 disease was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years. The average age of death for NPC1 disease was 16.2 years, with one-half of patients dying before the age of 12.5 years.” This information was from 87 questionnaires returned from the year long study in 2007. Because this disease is so rare most neurologists and geneticists have never treated a child or adult with this disease. So they too don't have many answers!

Brisan in May 2008 – The surgery that prompted testing for NPC.

How is it diagnosed?

Unfortunately there is no quick available test that will give you the answer. We spent almost three years in and out of doctors trying to figure out what this underlying puzzle piece was. Brisan had his tonsils and adenoids removed in May of 2008.  They noticed foamy macrophages which prompted the testing of NP-C.  If foamy macrophages appear it is a strong possibility of a Lysosomal Storage Disease. The test can take up to 6-8 weeks to receive the results from the blood work and skin biopsy that was collected. When you are told that your child or children have a fatal disease, this time period turns into an eternity of worried thoughts.

Treatments

There is no treatment for NP-C, but supportive therapies are available. These include medications to control seizures, abnormal posturing of limbs and tremors. Physical, speech and occupational therapy are also used to help with daily functioning. A low cholesterol diet and cholesterol-lowering medications do not appear to influence the course of this disease, and studies have shown no affect on the neurological progression. Currently a drug called Zavesca (Miglustat) which is FDA approved for Gaucher's Disease Type 1 (the most common Lysosomal Storage Disorder) is only available by mail through Curascript and is being used in NP-C patients off label.  Off label basically means that it is prescribed for a purpose outside the drug's orginal scope of approval. It has shown to help buy more time but the drug is not currently FDA approved in United States for use with Niemann Pick Type C Disease. This drug costs Brisan and Parker $190,000 per year (typically stated $159,000 per child). At this time our insurance company has been nice enough to cover this drug as long as our deductable has been met.

*Update on Zavesca: January 12, 2010 – http://www.npcfund.org/2009/12/historic-fda-related-drug-advisory-committee-will-meet-january-12th-2010-zavesca/

** Update on Zavesca: March 2010 – http://www.npcfund.org/2010/03/fda-says-hold-off-on-zavesca-miglustat-approval-they-want-more-information/

Autosomal Recessive Inheritance of NP-C

Genes are found in pairs within our body. We as parents pass one gene from every pair of genes to our children like Brisan and Parker. We inherited the affected genes from our ancestors on both sides of our family. From one generation to the next we simply have passed down these genes. Jennifer and I both carry one good copy of the NP-C gene and one affected copy of the NP-C gene on Chromosome 18.  Since we only carry one affected copy of the gene we are known as “carriers” and do not exhibit the disease.   Brisan and Parker received our affected copies of our NP-C gene which activates the symptoms on Niemann Pick Type C Disease. The below example shows in a basic manor what that means.

Autosomal Recessive Inheritance. Photo: Wikimedia Commons

Symptoms of Niemann Pick Type C Disease

• Enlarged liver and/or spleen
• Liver failure without neurological symptoms
• Difficulties with speech
• Development of dementia
• Seizures
• Jaundice at birth
• Early development of neurological problems
• Low muscle tone
• Delayed motor development beginning before age 2
• Sudden loss of muscle strength
• Progressive liver failure starting in infancy
• Early lung involvement without neurological disease

Side effects of Niemann Pick Type C Disease

When brain cell function is blocked NP-C children lose coordination (Gelastic Cataplexy), stumble, fall (Ataxia) and eventually need to be in wheelchairs, sleep in a hospital bed and utilize other adaptive equipment.  As the disease worsens other devastating symptoms develop including loss of the ability to speak (Aphasia), swallow (Dysphagia), laugh, remember (dementia), trouble moving eyes (Vertical Gaze Palsy) and often seizures occur.  The health of children with NPC deteriorates until ultimately, the disease claims the child’s life.