Niemann-Pick+Type+C

Audrey Stryker

**Niemann-Pick Type C** is a lysosomal storage disease. It is a rare and neglected fatal disease, with an estimated 500 cases worldwide in which the majority of the individuals die before age 20, and very few live past age 40. It is a genetic (recessive autosomal) neurodegenerative disorder with progressive deterioration of the nervous system and, eventually, death.

=**Flowchart:** =

Mutation on the NPC1 gene on chromosome 18.  [] ↓

The NPC1 gene encodes for the NPC1 protein that resides in the membrane of the lysosome.

 http://www.sciencedirect.com/science/article/pii/S1550413109001648

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The NPC1 protein mediates intracellular cholesterol transport from lysosomes.   []

↓ A mutation in the NPC1 gene encodes for a mutated NPC1 protein that leads to a deficiency in proper cholesterol and lipid transport from lysosomes.

 []

<span style="font-family: 'Times New Roman','serif'; font-size: 37.3333px;">↓ <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Failure to mobilize cholesterol results in a buildup of cholesterol in the cells, decreasing cell function. Cholesterol accumulation is shown in white. <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">[]

=<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Factsheet: =

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">organs/systems || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Accumulation of cholesterol in lysosomes decreases cell function as well as causing deficiency of cholesterol for membrane synthesis. Affects nervous system,brain, spleen, and liver. ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Name of disease || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Niemann-Pick Type C ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Root cause || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">A mutation on the NPC1 gene that codes for the NPC1 protein that mediates transport of cholesterol and lipids from the lysosome. ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Affected cell types/tissues/
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Historical background || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Albert Niemann first described the disease in 1914. Ludwig Pick described the pathology of the disease in the 1930’s. The disease was classified into types A, B, and C based on gene cause in 1961. In 2011, victims were shown to be resistant to Ebola virus because the virus could not be released from vesicles (Carette et al., 2011). ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Common symptoms || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Jaundice at birth, a child will begin to lose intellectual function, clumsiness, difficulty with eye movements, spleen or liver enlargement, slurred speech, seizures, loss of muscle strength, liver failure, and progressive neurodegeneration. ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Standard treatments || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Not yet a specific treatment. There are therapies including medicine for seizures; physical, speech, and occupational therapy. ||
 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Current research || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Researchers recently discovered that hydroxypropyl-beta-cyclodextrin has been shown to reduce cholesterol and lipid accumulation and may prolong survival. Clinical trials are underway. ||

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">References:
<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Alberts, B., Johnson, A. (2008). //Molecular Biology of the Cell// (5th ed). New York: Taylor and Francis.

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Ara Parseghian Medical Research Foundation. //About Niemann-Pick Type C//. Retrieved from []

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Carette JE, Raaben M, Wong AC, et al. (September 2011). "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1". //Nature// **477** (7364): 340–3.

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Meske, V., Erz, J., Priesnitz, T., and Ohm, T.G. (2014). The autophagic defect in Niemann-Pick disease type C neurons differs from somatic cells and reduces neuronal viability. //Neurobiology of Disease, 64//: 88-97.

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Niemann, A. (1914). "Ein unbekanntes Krankheitsbild". //Jahrbuch für Kinderheilkunde//. Neue Folge (Berlin) **79**: 1–10.

<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Pick, L. (1926). "Der Morbus Gaucher und die ihm ähnlichen Krankheiten (die lipoidzellige Splenohepatomegalie Typus Niemann und die diabetische Lipoidzellenhypoplasie der Milz)". //Ergebnisse der Inneren Medizin und Kinderheilkunde// (Berlin) **29**: 519–627.