Niemann–Pick Disease

Abstract

Niemann–Pick disease (NPD) encompasses at least three lysosomal storage disorders, all of which are inherited in an autosomal recessive manner. In NPD types A and B, the cause is a deficiency of acid sphingomyelinase (ASM), responsible for the hydrolysis of the sphingolipid sphingomyelin. In NPD type C (NPC), there is a deficiency of either a transmembrane (NPC1) or soluble nonenzymatic (NPC2) protein, both implicated in intracellular cholesterol transport. Secondary GM2-ganglioside storage in NPC may partly explain the associated neurodegenerative features. By definition, NPD type B is the nonneuronopathic form of the disease, whereas central nervous system involvement is a feature of NPD types A and C. The presence of a cherry-red spot is a characteristic feature of NPD type A, whereas supranuclear gaze palsy is noted in NPC. Currently, there is no specific therapy for NPD types A and B. Substrate synthesis inhibition (miglustat) has been shown to alter several signs (e.g., gaze palsy, swallowing difficulties) associated with NPC, although the ultimate neurological prognosis appears unchanged.