Niemann-Pick disease type C

Coined in the late 1920's from the pioneering work of Albert Niemann and Ludwig Pick, the eponym "Niemann-Pick disease" has since been used to designate a heterogeneous group of autosomal recessive lysosomal lipid storage disorders, with common features of hepatosplenomegaly and sphingomyelin storage in reticuloendothelial and parenchymal tissues, with or without neurological involvement. In 1958, Crocker and Farber showed that there was a wide variability in age of onset and clinical expression, as well as in the level of sphingomyelin storage in tissues [1]. This led Crocker to propose a classification into four subgroups, A to D [2]. Type A was characterized by severe, early CNS deterioration and massive visceral and cerebral sphingomyelin storage. Type B showed a chronic course with marked visceral involvement but a sparing of the nervous system. Types C and D were characterized by a sub acute nervous system involvement with a moderate and slower course and a milder visceral storage. Type D patients were individualized essentially on their homogenous Nova Scotia Acadian origin. In 1966, Brady and associates [3] demonstrated a severe deficiency in sphingomyelinase activity in tissues from patients with type A, a finding soon extended to type B, but not to types C and D, indicating that the two latter types constituted separate entities. From that time on, with a turn following seminal observations in a Balb/c murine model of the disorder [4], the concept of Niemann-Pick type C disease evolved from that of a sphingomyelin storage disorder to that of a cholesterol storage disorder [5]. This and later work led to the reclassification of type C as a cellular lipid trafficking disorder, involving more specially, but not only, endocytosed cholesterol.Today, by definition, "Niemann-Pick C disease" encompasses disorders characterized by unique abnormalities of intracellular transport of endocytosed cholesterol with sequestration of unesterified cholesterol in lysosomes a