Niemann-Pick Disease

Niemann-Pick disease comprises a group of autosomal recessive lysosomal storage disorders affecting sphingomyelin and cholesterol metabolism. Type A and B result from SMPD1 gene mutations affecting acid sphingomyelinase, while Type C results from mutations in NPC1 or NPC2 genes affecting cholesterol trafficking. In all types, lipids accumulate progressively in lysosomes throughout the body. Type A presents as severe neurovisceral disease in infancy with hepatosplenomegaly, developmental regression, and early death, usually by age 3. Type B has hepatosplenomegaly and pulmonary involvement but typically preserved cognitive function. Type C has more variable presentation with progressive neurological disease, vertical supranuclear gaze palsy (a hallmark finding), liver disease, and pulmonary involvement. Without treatment, Type C patients often become severely disabled in adolescence or adulthood. Miglustat, an inhibitor of glucosylceramide synthase, can slow neurological progression in Type C disease.