Der Nervenarzt

, Volume 74, Issue 10, pp 900–905

Morbus Niemann-Pick Typ C

Eine neurometabolische Erkrankung durch Störung des intrazellulären Lipidtransports
Ergebnisse und Kasuistik

Zusammenfassung

Der Morbus Niemann-Pick Typ C (NPC) ist eine seltene neuroviszerale Lipidspeicherkrankheit, die auf genetischen Defekten lipidtransportierender Proteine beruht. NPC ist von den Morbus Niemann-Pick Typen A und B (Sphingomyelinlipidosen) pathogenetisch verschieden und gekennzeichnet durch genetische (Mutationen in NPC1 oder NPC2[=HE1]Gen), biochemische und insbesondere klinische Heterogenität. Am häufigsten ist ein spät-infantiler bis juveniler Verlaufstyp mit Verhaltensauffälligkeiten, Ataxie, Dysarthrie, Dysphagie, Dystonie, Kataplexie, vertikaler Blickparese, Splenomegalie und demenzieller Entwicklung. Bei adulten Varianten stehen oft Demenz oder Psychosen im Vordergrund, fakultativ bestehen Dysarthrie, Ataxie, Splenomegalie oder vertikale Blickparese. Routinelaborparameter einschließlich Serumcholesterin sind regelrecht. Im Knochenmarksausstrich finden sich oft sog. "seeblaue Histiozyten", seltener Schaumzellen. Zur Diagnosesicherung ist der Nachweis einer Cholesterinanhäufung in perinukleären Lysosomenäquivalenten und einer verminderten Cholesterinveresterung nach Beladung mit exogenem LDL-Cholesterin in Fibroblasten erforderlich.Die Behandlung beschränkt sich auf symptomatische Maßnahmen.

Schlüsselwörter

Morbus Niemann-Pick Lipidspeicherkrankheit Mutationsanalyse Klinische Heterogenität Therapie 

Summary

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.

Keywords

Niemann-Pick disease Lipid storage disorder Mutational analysis Clinical heterogeneity Therapy 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Neurologische KlinikUniversität Heidelberg
  2. 2.Psychiatrische KlinikUniversität Heidelberg
  3. 3.Neurometabolisches LaborUniversitätskinderklinik Tübingen
  4. 4.Neurologische KlinikStädtisches Klinikum LudwigshafenLudwigshafen

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