“They Only Have a Childhood To Live a Lifetime”

“A rare disease, sometimes known as an orphan disease, is any disease that is not common.” (wikipedia.org)

Orphan disease: A disease which has not been "adopted" by the pharmaceutical industry because it provides little financial incentive for the private sector to make and market new medications to treat or prevent it. (MedicineNet.com)

http://rarediseases.info.nih.gov/RareDiseaseList.aspx

First what is a Rare Disease?

Niemann-Pick Type C (NPC) affects 1 out of 150,000 births. Since it is so rare, statistically it is difficult to truly measure.

1 of over 7,000 rare diseases. Roughly only 200 have some type of manageable treatment.

Niemann-Pick Type C Disease (NP-C) is a genetic pediatric neurodegenerative disorder causing progressive deterioration of the nervous system because of the cells inability to metabolize cholesterol. One of 50-60 Lysosomal Storage Disorders.

It usually starts to affect children of school age (4-7 years old) by interfering with their ability to metabolize cholesterol within the cell. Adult onset may occur.

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.

Found on Chromosome 18NPC1 & NPC2 Gene

Quick History of Niemann-Pick

There are 3 types of Niemann-Pick Disease. Types A, B, and C.

In 1914 Albert Niemann, A German pediatrician, described a young child with an enlarged liver and spleen, enlarged lymph glands, swelling and a darkening of the skin of the face. The child had brain and nervous system impairment and died in less than six months, before the age of two. Later, in the 1920's, Luddwick Pick studied tissues after the death of such children and provided evidence of a new disorder, distinct from those storage disorders previously described. (www.ntsad.org)

Albert Niemann published the first description of what is now known as Niemann-Pick disease, type A, in 1914. (wikipedia.org)

Ludwig Pick described the pathology of the disease in a series of papers in the 1930s. (wikipedia.org)

Autosomal Recessive Inheritance. Photo: Wikimedia Commons

Autosomal Recessive Inheritance of NP-C

You have a 1 in 4 chance with each pregnancy

Genes are the blueprints for making the substances, called proteins, our bodies need to develop and work properly.

Most genes come in pairs, one of which is inherited from the mother and the other from the father. A mutation is a change in a gene that prevents it from working properly.

Mutations in genes are inherited from our biological parents in specific ways. One of the basic patterns of inheritance of our genes is called autosomal recessive inheritance. (University of Virginia Health System)

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.

Approximately 500 cases have been diagnosed worldwide ever. Currently there are less than a 100 people in the US.

The transport of cholesterol in the cells is studied by measuring conversion of the cholesterol from one form to another ("esterification"). The storage of cholesterol is assessed by staining the cells with a chemical ("filipin") that glows under ultraviolet light. This can show whether the cholesterol is being stored inappropriately in lysosomes, the recycling centers of the cell. It is important that both the transport and storage tests be performed, since reliance on one or the other may lead to an incorrect diagnosis or a missed diagnosis of a variant form of NPC. (www.nnpdf.org)

It can be determined by taking a small piece of skin ("skin biopsy"), growing the cells ("fibroblasts") in the laboratory, and studying their ability to transport and store cholesterol. (www.nnpdf.org)

Unfortunately there is no quick available test that will give you the answer.

How is it diagnosed?

Foamy Macrophages: Webpathology.com

Treatments

No magic pill nor treatment are currently available to cure.

Supportive therapies include physical, occupational, and speech therapies.

Medication to control seizures, abnormal posturing of limbs, and tremors.

Zavesca (Miglustat) is a FDA approved drug being used for mild to moderate type 1 Gaucher Disease. Currently being used “off label” meaning it is not FDA approved for Niemann-Pick Type C in the US.

Zavesca is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for the first step in the synthesis of most glycosphingolipids. (www.rxlist.com)

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.

References:

University of Virginia Health Systemshttp://www.healthsystem.virginia.edu/UVAHealth/hub_cancer/ari.cfm

National Niemann Pick Disease Foundation www.nnpdf.org

Ara Parseghian Medical Research Foundation www.parseghian.org

PubMed.gov http://www.ncbi.nlm.nih.gov/pubmed/17497724?dopt=Abstract

MedicineNet.org www.medicinenet.org

Niemann-Pick Children’s Fund www.NPCFund.org

NTSADhttp://www.ntsad.org/S02/S02Niemann-Pick.htm

Thank You for taking time to view this information!

To donate to help further research, education/awareness, and family services please visit:http://www.npcfund.org/donate.html