title: Mechanisms of hypercholesterolaemia in glycogen storage disease type I: defective metabolism of low density lipoprotein in cultured skin fibroblasts.
abstract: Hyperlipidaemia is a feature of glycogen storage disease type I (GSD-I) (Levy et al.). High levels of LDL cholesterol (200 +/- 25 mg dl-1) and apo B (387 +/- 44 mg dl-1) were found in association with hypercholesterolaemia in GSD-I. Related causative factors might be attributed to overproduction and/or delayed removal of LDL. In this study, a possible alteration in the clearance of LDL was examined. Using cultured fibroblasts for LDL receptor activity, the following observations were made: 1. GSD-I fibroblasts revealed only a slight decrease in LDL binding (65 +/- 7) when compared with controls (74 +/- 4 ng mg-1 protein), however, LDL internalization (382 +/- 24 vs. 570 +/- 52 ng mg-1 protein) and proteolytic degradation (2082 +/- 280 vs. 2916 +/- 12.5 ng mg-1 protein) were significantly affected (P less than 0.01). 2. Binding, internalization and proteolytic degradation of LDL from GSD-I were compared with that of controls, and were found to be significantly lower (P less than 0.01). 3. Substitution of control lipoprotein-deficient serum (LPDS) by GSD-I LPDS further diminished the above processes (P less than 0.05). Our results demonstrate that increased plasma cholesterol in GSD-I is due to a decreased catabolism of LDL. The data suggest that the problem may well be multifactorial, due to diminished receptor expression, abnormal LDL composition and impaired LDL receptor interaction due to a circulating inhibitory factor.
authors.affiliation: Department of Nutrition, University of Montreal, Quebec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Levy
authors.forename: L
authors.initials: L
authors.lastname: Thibault
authors.forename: C C
authors.initials: CC
authors.lastname: Roy
authors.forename: J
authors.initials: J
authors.lastname: Letarte
authors.forename: M
authors.initials: M
authors.lastname: Lambert
authors.forename: E G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000150:complications* / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D011973:Receptors, LDL / Q000378:metabolism; D012867:Skin / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL