Clinical Information

Niemann-Pick disease (NPD) types A (NPA) and B (NPB) are autosomal recessive lysosomal storage disorders affecting metabolism of specific lipids within cells. NPA and NPB are caused by a deficiency of sphingomyelinase, which results in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. NPA disease is more severe than NPB and is characterized by early onset with feeding problems, dystrophy, persistent jaundice, development of hepatosplenomegaly, neurological deterioration, deafness, and blindness, leading to death by age 3. NPB disease is limited to visceral symptoms with survival into adulthood. Some patients have been described with intermediary phenotypes. Large lipid-laden foam cells are characteristic of the disease. Approximately 50% of cases have cherry-red spots in the macula.

The combined prevalence of NPA and NPB is estimated to be 1 in 250,000. NPA and NPB are inherited in an autosomal recessive manner and are caused by variants in the SMPD1 gene. Although there is a higher frequency of type A among the Ashkenazi Jewish population, both types are panethnic. Individuals with NPD types A and B typically have elevations of lyso-sphingomyelin and lyso-sphingomyelin 509 combined with elevations of the oxysterols cholestane-3 beta, 5 alpha, 6 beta-triol (COT) and 7-ketocholesterol (7-KC). (OXNP / Oxysterols, Plasma; OXYWB / Oxysterols, Blood; OXYBS / Oxysterols, Blood Spot). Molecular genetic testing for NPA and NPB disease is also available (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specifcy SMPD1 Gene List ID: IEMCP-W6S9XD).