Niemann-Pick Disease, Type C

Niemann-Pick Disease Type C (NPC) is a rare lipid storage disorder that is characterized by accumulation of LDL-derived cholesterol in lysosomes. This abnormality leads to progressive neurological deterioration, visceral symptoms and premature death. Neurologic abnormalities gradually develop, including ataxia, spasticity, seizures, dysarthria and dysphagia. Other features presenting later in life may include dystonia and vertical [...]

Niemann-Pick Disease Type C (NPC) is a rare lipid storage disorder that is characterized by accumulation of LDL-derived cholesterol in lysosomes. This abnormality leads to progressive neurological deterioration, visceral symptoms and premature death. Neurologic abnormalities gradually develop, including ataxia, spasticity, seizures, dysarthria and dysphagia. Other features presenting later in life may include dystonia and vertical supranuclear gaze palsy, dementia and psychiatric manifestations. Hepatomegaly and/or splenomegaly may or may not be present. The age and severity of onset can vary widely. The biochemical diagnosis can be made on cultured skin fibroblasts by evaluating LDL-derived cholesterol esterification and/or with filipin staining showing intracellular accumulation of cholesterol. Two genes are associated with NPC. Mutations in the NPC1 and NPC2 genes result in similar clinical and biochemical phenotypes but can be distinguished by complementation group. NPC1 represents the major complementation group and is due to mutations in the NPC1 gene whereas NPC2 is caused by mutations in the NPC2/HE1 gene. Mutations in NPC1 are responsible for approximately 95% of Niemann-Pick Type C cases, while approximately 4-5% of patients have mutations in the NPC2/HE1 gene.