Niemann-Pick disease (NPD)
by Alexander Kurz
Nieman-Pick disease (NPD) refers to a heterogenous group of disorders the common features of which include autosomal recessive inheritance, hepatosplenomegaly, and accumulation of variable amounts of sphingomyelin and other lipids in liver, spleen, and bone marrow.
NPD is separated into disorders associated with marked deficiency of sphingomyelinase and prominent storage of sphingomyelin (Types A, B, and F) and disorders in which spingomyelinase activity is mildly reduced or normal (Types C, D, and E). Lipid accumulation in these patients was recently related to impaired esterification of intracellular cholesterol.
Symptoms and course
The neurological features of NPD type C include organomegaly, dementia, ataxia, supranuclear opthalmoplegia and dystonia. Onset usually occurs in childhood with psychomotor retardation most typically manifested as poor school performance. Focal or generalised seizures may occur as a late complication. Onset in adolescence or adulthood is associated with a slower rate of disease progression, and organomegaly is less prominent.
Causes and risk factors
The central biochemical defect is a deficiency in sphingomyelinase which results in a blockade of cholesterol esterification. As a consequence, abnormal amounts of unesterified cholesterol is stored.
However, nerve cells demonstrate not only storage of cholesterol but also neurofibrillary tangles. Tangles are found in many parts of the brain. Tangles are silver-staining and react strongly with antibodies to tau protein. Ultrastructurally the tangles consist of paired helical filaments identical to those seen in Alzheimer’s disease. Niemann-Pick disease is genetically heterogeneous. Type C1 is caused by mutations in the NPC1 gene on chromosome 18 (18q11.q12).
The cranial CT may be normal despite significant neurological symptoms. The diagnosis can be confirmed by the demonstration of an impaired ability of culutred skin fibroblasts to esterify exogenous cholesterol or by the finding of elevated levels of sphingomyelin, cholesterol, or glycolipid in the spleen or liver. Bone marrow aspiration commonly shows the presence of foam cells.
Care and treatment
There is no effective treatment.
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Last Updated: lundi 10 août 2009