Niemann-Pick type C disease (NP-C) presents with heterogeneous neurological and psychiatric symptoms. Adult onset is rare and possibly underdiagnosed due to frequent lack of specific and obvious key symptoms. For both early and adolescent/adult onset, the available data from studies and case reports describe a positive effect of Miglustat (symptom relief or stabilization). However, due to the l...

Niemann-Pick disease type C2 (NP-C2) is a fatal hereditary disease characterized by accumulation of low-density lipoprotein-derived cholesterol in lysosomes. Here we report the 1.7-A resolution crystal structure of the cholesterol-binding protein deficient in this disease, NPC2, and the characterization of its ligand binding properties. Human NPC2 binds the cholesterol analog dehydroergosterol ...

BACKGROUND Niemann-Pick disease and β-thalassemia are distinct conditions with specific clinical and morphological manifestations. β-thalassemia is the most common inherited blood disorder in Iran whereas Niemann-Pick disease, a lysosomal storage disorder, is rarely found in this country. CASE PRESENTATION This 5-month old girl, a known case of β-thalassemia major was hospitalized for failure...

We present 2 cases of Niemann Pick disease, type B with secondary sea-blue histiocytosis. Strikingly, in both cases the Pick cells were positive for tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher cells. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

Alzheimer's disease (AD) and Niemann-Pick type C (NPC) disease are progressive neurodegenerative diseases with very different epidemiology and etiology. AD is a common cause of dementia with a complex polyfactorial etiology, including both genetic and environmental risk factors, while NPC is a very rare autosomal recessive disease. However, the diseases share some disease-related molecular path...

Familial hypercholesterolemia (FH), Niemann-Pick disease type C (NPC) and Tangier disease (TD) are genetic inherited disorders with impaired processing of cholesterol, caused by mutations in genes that regulate cellular uptake, intracellular movement and transport of cholesterol. Various studies have shown a crucial regulatory role of the SREBP-pathway for cellular cholesterol homeostasis in th...

Niemann-Pick type C1 (NPC1) disease results from a defect in the NPC1 protein and is characterized by a pathological accumulation of cholesterol and glycolipids in endocytic organelles. We followed the biosynthesis and trafficking of NPC1 with the use of a functional green fluorescent protein-fused NPC1. Newly synthesized NPC1 is exported from the endoplasmic reticulum and requires transit thro...

Type C Niemann-Pick disease is due to a mutation in Niemann-Pick C (NPC) protein, a putative determinant of intracellular cholesterol transport. This study quantifies cholesterol balance in vivo across all tissues in mice with this defect. Cholesterol balance in the heterozygous animal is normal, but in the homozygous mouse the whole animal cholesterol pool expands continuously from birth, reac...

Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-...

The lipid changes in the inheritable foam cell reticulosis of mice discovered by Lyons, Hulse, and Rowe have been reexamined. The major abnormality in thymuses from homozygous-abnormal animals has been identified as an increase in the concentration (per milligram of protein) of sphingomyelin and cholesterol. This increase is associated with normal sphingomyelin-cleaving activity. The lipid comp...