title: Cholesteryl Ester Storage Disease (CESD) due to novel mutations in the LIPA gene.
abstract: Cholesteryl Ester Storage Disease (CESD) is a rare recessive disorder due to mutations in LIPA gene encoding the lysosomal acidic lipase (LAL). CESD patients have liver disease associated with mixed hyperlipidemia and low plasma levels of high-density lipoproteins (HDL). The aim of this study was the molecular characterization of three patients with CESD. LAL activity was measured in blood leukocytes. In two patients (twin sisters) the clinical diagnosis of CESD was made at 9 years of age, following the fortuitous discovery of elevated serum liver enzymes in apparently healthy children. They had mixed hyperlipidemia, hepatosplenomegaly, reduced LAL activity (approximately 5% of control) and heteroalleic mutations in LIPA gene coding sequence: (i) the common c.894 G>A mutation and (ii) a novel nonsense mutation c.652 C>T (p.R218X). The other patient was an 80 year-old female who for several years had been treated with simvastatin because of severe hyperlipidemia associated with low plasma HDL. In this patient the sequence of major candidate genes for monogenic hypercholesterolemia and hypoalphalipoproteinemia was negative. She was found to be a compound heterozygote for two LIPA gene mutations resulting in 5% LAL activity: (i) c.894 G>A and (ii) a novel complex insertion/deletion leading to a premature termination codon at position 82. These findings suggest that, in view of the variable severity of its phenotypic expression, CESD may sometimes be difficult to diagnose, but it should be considered in patients with severe type IIb hyperlipidemia associated with low HDL, mildly elevated serum liver enzymes and hepatomegaly.
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, I-16132 Genoa, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fresa
authors.forename: Antonella
authors.initials: A
authors.lastname: Bellocchio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pino
authors.forename: Virgilia
authors.initials: V
authors.lastname: Guido
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cantafora
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
mesh_terms: D000293:Adolescent; D000369:Aged, 80 and over; D015217:Cholesterol Ester Storage Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D002787:Sterol Esterase / Q000235:genetics*
chemical_list: D008055:Lipids; C503451:LIPA protein, human; D002787:Sterol Esterase