[Niemann-Pick disease type C--a neurometabolic disease through disturbed intracellular lipid transport].
Niemann-Pick disease type C (NPC) is a rare, neurovisceral lipid storage disorder caused by genetic defects in lipid transporting proteins. It is distinct from Niemann-Pick types A and B (sphingomyelin lipidoses) and displays genetic (mutations in the NPC1 or NPC2[=HE1] gene), biochemical, and clinical heterogeneity. Late infantile to juvenile forms of NPC predominate and are characterised by atypical behaviour, ataxia, dysarthria, dysphagia, dystonia, cataplexy, vertical gaze palsy, splenomegaly, and dementia. In adult variants, psychosis and dementia are common, and dysarthria, ataxia, splenomegaly, and vertical gaze palsy are further facultative signs. Routine laboratory results including serum cholesterol are normal. In bone marrow smears, sea-blue histiocytes are often demonstrated and foam cells sometimes seen. The diagnosis is confirmed by detecting free cholesterol accumulation in perinuclear granules (lysosomes) and reduced cholesterol esterification after challenge with exogenous low-density lipoprotein in fibroblasts. Alternatively or additionally, mutational analysis can be performed. Treatment is restricted to symptomatic measures, since there is no specific therapy.
Grau
A J
AJ
Neurologische Klinik, Universität Heidelberg, graua@klilu.de
Weisbrod
M
M
Hund
E
E
Harzer
K
K
D000328:Adult; D001284:Atrophy; D001853:Bone Marrow / Q000473:pathology; D001921:Brain / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004252:DNA Mutational Analysis; D003704:Dementia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics; D009460:Neurologic Examination; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D012618:Sea-Blue Histiocyte Syndrome / Q000473:pathology; D013107:Sphingolipids / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D013107:Sphingolipids; D033921:Vesicular Transport Proteins; D002784:Cholesterol