The demonstration of a defect of cholesterol esterification in a mutant strain of BALB/c mice with an attendant reduction of sphingomyelinase activity [Pentchev, P. G., Boothe, A. D., Kruth, H.S., Weintroub, H., Stivers, J. & Brady, R. O. (1984) J. Biol. Chem. 259, 5784-5791] prompted us to examine the capacity of cultured human Niemann-Pick fibroblasts to esterify exogenously derived cholester...

NAKASHIMA, M., KUDOH, T., SUKEGAWA, .K., MARUYAMA, K. and ORII, T. Metabolism of Sphingomyelin in Cultured Skin Fibroblasts from Patients with Different Types of Niemann-Pick Disease. Tohoku J. exp. Med., 1986, 148 (4), 365-371 The metabolism of [choline-methyl-14C] sphingomyelin in cultured skin fibroblasts from patients with different types of Niemann-Pick disease was measured 1 and 3 days af...

Lysosomal storage disorders (LSD) are characterized by the accumulation of diverse lipid species in lysosomes. Niemann-Pick type A/B (NPA/B) and type C diseases Niemann-Pick type C (NPC) are progressive LSD caused by loss of function of distinct lysosomal-residing proteins, acid sphingomyelinase and NPC1, respectively. While the primary cause of these diseases differs, both share common biochem...

Mutations in the Niemann-Pick disease genes cause lysosomal cholesterol accumulation and impaired low density lipoprotein (LDL) cholesterol esterification. These findings have been attributed to a block in cholesterol movement from lysosomes to the site of the sterol regulatory machinery. In this study we show that Niemann-Pick type C1 (NPC1) and Niemann-Pick type C2 (NPC2) mutants have increas...

Familial lipodystrophic conditions, such as Gaucher's, Niemann-Pick, and Tay-Sachs disease, are characterized by the intracellular accumulation of abnormally large quantities of sphingolipids. In Gaucher's disease, the offending lipids are cerebrosides, while Niemann-Pick and Tay-Sachs diseases are characterized by the accumulation of sphingomyelin and gangliosides, respectively. In Gaucher's a...

Hemophagocytic lymphohistiocytosis (HLH) is a disease characterized by phagocytosis of blood cells by macrophages within the lymphoreticular tissue. It can develop secondary to some diseases or be familial as a result of genetic mutations. Niemann-Pick disease (NPD) is a very rare lipid storage disease. A three-month-old girl presented with high fever (39°C), abdominal distension and paleness. ...

The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in...

Niemann-Pick Type C disease is a homozygous recessive disorder resulting in errant intracellular cholesterol metabolism and the accumulation of intracellular unesterified cholesterol and sphingolipids. Although no current effective treatment exists for Niemann-Pick Type C disease, a number of therapies are under development in animal models. As therapies are brought into clinical trials, it wil...

A patient with Niemann-Pick disease is reported together with family studies. Her liver and bone marrow were shown to be infiltrated with sea blue histiocytes. Other organs, spleen and lung, were presumably also involved but histological proof was not obtained. Enzyme assay of leucocytes, lymphocytes, and cultured skin fibroblasts showed the patient to be deficient in sphingomyelinase activity....