Gasche, C and Aslanidis, C and Kain, R and Exner, M and Helbich, T and Dejaco, C and Schmitz, G and Ferenci, P (1997) A novel variant of lysosomal acid lipase in cholesteryl ester storage disease associated with mild phenotype and improvement on lovastatin. JOURNAL OF HEPATOLOGY, 27 (4). pp. 744-750. ISSN 0168-8278,
Full text not available from this repository.Abstract
Cholesterol ester storage disease (CESD) is a rare congenital disorder of lipid metabolism, with mutation of the lysosomal acid lipase gene, causing chronic liver disease, usually before adolescence, We here describe three adult siblings with CESD diagnosed by light microscopic demonstration of excessive lysosomal storage of lipids with accumulation of foamy cells in liver biopsies and by a decrease in acid lipase activity (2-3% of controls), One patient (male, 46a) had extensive liver fibrosis, another (female, 58a) had cirrhosis of the liver, The third patient had died from variceal haemorrhage (female, 56a), Using sequence analysis of RT-PCR products of LAL mRNA, the patients were identified as compound heterozygotes for a G-->A substitution at position -1 of the exon 8 splice donor site and a point mutation at the second allele, resulting in a His(108)-->Pro shift, In two patients, therapy with lovastatin was initialed, which led to normalisation of serum cholesterol and triglyceride levels, After 12 months, liver biopsy demonstrated a significant decrease in vacuolisation of hepatocytes, with fewer and smaller droplets, Semi-automated computer-assisted image analysis of electron microscopic sections demonstrated a decrease in the hepatocellular lysosomal area from 20.5+/-7.1% to 11.7+/-6.5% (p<0.05) and 41.7+/-5.1% to 33.4+/-4.4% (p<0.01), We conclude that in two siblings with a novel LAL variant and mild phenotype of CESD, lovastatin decreased both serum lipid concentrations and hepatocellular lysosomal content.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SPLICE JUNCTION MUTATION; WOLMAN-DISEASE; GENE; DEFICIENCY; LIVER; CESD; DELETION; THERAPY; cholesterol ester storage disease; lovastatin; lysosomal acid lipase |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/50525 |
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