Niemann-Pick Disease

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Niemann-Pick disease, of which there are several types (A, B, C, and D) belongs to a group of fatal lysosome storage diseases (LSDs) affecting metabolism. The first description of Niemann-Pick Disease type A (NPA) was published by physician Albert Niemann in 1914. German neuropathologist Ludwig Pick published a series of papers in the 1930’s describing the disease’s pathology. While Niemann-Pick disease can be found amongst all racial and ethnic groups, type A is most commonly found amongst Jewish individuals of Ashkenazi (Eastern European) descent. Type B (NPB) is also found among Ashkenazi Jews, albeit to a lesser extent.

The cause of NPA is an enzymatic deficiency, specifically the enzyme acid sphingomyelinase (ASM), which is located within lysosomes. The function of ASM is to metabolize the lipid sphingomyelin, and when it is absent or present in insufficient amounts, the result is cell death and major organ system malfunction. People with NPA produce little to no ASM. In addition, NPA is the most severe type of Niemann-Pick disease, and it primarily affects the neurological system.


Over 95% of cases of NPA are caused by mutations R496L, fsP330, and L302P in the SMPD1 gene. An inherited disease, it is autosomal recessive, meaning both copies of the gene must exhibit the mutation in order for the individual to be afflicted. A child with two carrier parents has a 1 in 4 chance of being afflicted with NPA or NPB.


Symptoms of Niemann-Pick disease are generally manifested in the organs where lipids have accumulated. In the case of NPA, lipids tend to accumulate in the brain, the cerebellum in particular, and the nervous system. This leads to difficulty swallowing, an unsteady gait, and slurred speech. Other possible symptoms include loss of muscle tone, especially during laughter, sleep inversion, seizures, and loss of mental capabilities. With NPB, lipids generally accumulate in the liver and spleen, causing respiratory problems and cardiovascular stress.

Prognosis and Treatment

As there is no cure or direct treatment for NPA, it is always fatal, and NPA patients generally die between the ages of 2 and 4. Those afflicted with NPB, however, can survive into late childhood or young adulthood. Management of NPA and NPB symptoms may come from physical therapists, gastroenterologists, nephrologists (liver specialists), pulmonologists, cardiologists, and nutritionists.

This post is part of the series: The Ashkenazi Jewish Genetics Panel

This series describes the diseases tested for in the Ashkenazi Jewish Genetics Panel (AJGP).

  1. What is the Ashkenazi Jewish Genetic Panel?
  2. Bloom’s Syndrome
  3. Canavan Disease
  4. Familial Dysautonomia (FD)
  5. Fanconi Anemia (FA)
  6. Gaucher Disease
  7. Mucolipidosis IV
  8. Niemann-Pick Disease
  9. Torsion Dystonia