Niemann Pick Disease Type A and B: SMPD1 Recurrent Mutations

Niemann disease types A and B (NP) are lysosomal storage disorders resulting from the accumulation of sphingomyelin, cholesterol and other lipids in the cells of affected individuals due to a deficiency of sphingomyelinase activity. Niemann Pick type A (NPA) presents in infancy with organomegaly and rapid neurodegeneration leading to death by ~3 years of age. Niemann Pick type B (NPB) is clinically heterogeneous and individuals can present with multiple findings including hepatosplenomegaly, growth delay, frequent respiratory infections, fatigue and hematologic abnormalities. Individuals with NPB usually survive into adulthood. DNA testing for three mutations common in the Ashkenazi Jewish population for NPA and one mutation in NPB is performed. NP is an AR disorder caused by mutations in the SMPD1 gene, located on chromosome 11 (11p15.4). Four mutations in the SMPD1 gene account for greater than 95% of the mutations seen in AJ individuals affected with Niemann Pick disease, type A & B.

See related information sheet: Ashkenazi Jewish Screening Panel