Concurrent increase of cholesterol, sphingomyelin and glucosylceramide in the spleen from non‐neurologic Niemann–Pick type C patients but also patients possibly affected with other lipid trafficking disorders

FEBS Letters

Fröhlich, Eckhart³  Massenkeil, Gero¹  Harzer, Klaus² 

[1] Abteilung für Hämatologie und Onkologie, Charité, Campus Virchow-Klinikum Berlin, 13353 Berlin, Germany;Institut für Hirnforschung, Universität Tübingen, Calwer Strasse 3, 72076 Tübingen, Germany;Innere Klinik 1, Abteilung für Gastroenterologie, Karl-Olga-Krankenhaus Stuttgart, D-70190 Stuttgart, Germany

关键词: Niemann–Pick type C disease;    Spleen lipid;    Cholesterol;    Sphingolipid;    Ceramide;    Raft;    Acc-CSG;    combined accumulation of cholesterol;    sphingomyelin and glucosylceramide;    NPC;    Niemann–Pick type C disease;    NPC1 and NPC2 (=HE1);    the two NPC genes;    and the respective proteins NPC1 and HE1;    TLC;    thin-layer chromatography;   

DOI  :  10.1016/S0014-5793(03)00100-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Niemann–Pick type C disease (NPC) is a neurovisceral (or, extremely rarely, only visceral) lipidosis caused by mutations in the NPC1 gene or, in a few patients, the HE1 gene, which encode sterol regulating proteins. NPC is characterised by a complex lipid anomaly including a disturbed cellular trafficking of cholesterol but also multi-lipid storage in visceral organs and brain. Lipids were studied using conventional methods in enlarged spleens that had been removed from five patients for different therapeutic and diagnostic reasons and found to have microscopic signs of lysosomal storage disease not suspected clinically. The spleen lipid findings with a concurrent accumulation of cholesterol, sphingomyelin and glucosylceramide (Acc-CSG) allowed us to suggest NPC diagnoses for these patients, who were free of neurologic symptoms. From two patients no material for confirmatory studies was available, but in two other patients NPC diagnoses could be confirmed with the filipin cytochemical cholesterol assay and NPC1 gene analysis, respectively. However, these tests and also HE1 gene analysis were negative in a third patient. Since the Acc-CSG lipid pattern seems to indicate a multi-lipid trafficking defect rather than being highly specific for NPC, this patient, if not affected with very atypical NPC, may be a candidate for a different lipid trafficking disorder. The Acc-CSG pattern was considered to be similar to the lipid pattern known for the lipid rafts, these functional cell structures being probably disorganised and accumulated in late endosomes and lysosomes of NPC cells.

【 授权许可】

Unknown