Defects in the degradation of sphingomyelin are a group of autosomal recessive lysosomal storage diseases including Niemann-Pick disease (NPD), type A/B and Farber lipogranulomatosis. NPD is caused by deficient acid sphingomyelinase (ASM) activity, and Farber lipogranulomatosis is caused by acid ceramidase deficiency, resulting in accumulation of sphingomyelin, ceramide and cholesterol in many organs. ASM and acid ceramidase are key enzymes of the two steps degradation of sphingomyelin and play important roles in normal membrane turnover.
NPD typeA is the infantile form characterized by a rapidly progressive neurodegenerative course that leads to early death. NPD typeB is the later-onset form in which patients exhibit little or no neurological symptoms, but may have severe and progressive visceral organ abnormalities, including hepatosplenomegaly and cardiovascular disease. The different clinical presentations of Types A and B NPD are likely due to small differences in the amount of residual, functional ASM activity.
