[Niemann-Pick disease types A and B].

The molecular basis of Niemann-Pick disease, type A and B, has been confirmed by detection of mutations causing deficiency of the acid sphingomyelinase activity in the patients. It has been shown that mutations, which cause no activity of acid sphingomyelinase, are responsible for the type A and mutations which cause residual activities of the enzyme are responsible for the type B. Acid sphingomyelinase deficient mice have been established and confirmed to show a similar abnormality observed in human disease type A. These knock-out mice should serves as a useful model for somatic gene therapy. The mechanism of neuronal cell dysfunctions in the type A patients has not been well-characterized. Progress suggest that ceramide, which is produced by sphingomyelinase from sphingomyelin, is an important factor for signal transduction of cell differentiation. In addition, a lysosphingolipid (sphingosylphocholine), which accumulates in the tissues of the patients, has been reported to act as a strong mitogen in several types of cells through activating a transcription factor. AP-1. It is possible that abnormal phospholipid signaling is involved in the pathogenesis of neuronal cell dysfunction of Niemann-Pick disease type A.