title: [Lysosomal acid lipase deficiency. Overview of Czech patients].
abstract: Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage of triacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediated LDL endocytosis are affected (liver, kidneys). There are two basic phenotypes. The fatal infantile phenotype (Wolman's disease) with generalized storage of both types of apolar lipids. This form was diagnosed in this country only once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterized by the storage of CE (which gave this entity the name of cholesteryl storage disease--CESD). Its main sign is affection of the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotic transformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increased VLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipids is a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases of CESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy with hepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patients with permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quite incidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis was established in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) and molecular genetic level (mutation in enzyme locus). In all instances mutation of G934A was found leading to reduction and loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations were heterozygous. In one instance for technical reasons only one allele was analyzed. In three instances a point "missense" mutation was found: T323A (Trp74Arg), T4(75)A (Asp124Glu), A210T (Asp36Gl), in one instance a "nonsense" mutation: C233T (Arg44-stop) and twice a deletion mutation delta C673-5 and delta G1068-8 leading to impairment of the reading frame and to premature stop of the codon.
authors.affiliation: Ustav dĕdicných poruch metabolismu 1. LF UK, Praha.
authors.forename: M
authors.initials: M
authors.lastname: Elleder
authors.forename: H
authors.initials: H
authors.lastname: Poupĕtová
authors.forename: J
authors.initials: J
authors.lastname: Ledvinová
authors.forename: J
authors.initials: J
authors.lastname: Hyánek
authors.forename: J
authors.initials: J
authors.lastname: Zeman
authors.forename: J
authors.initials: J
authors.lastname: Sýkora
authors.forename: F
authors.initials: F
authors.lastname: Stozický
authors.forename: A
authors.initials: A
authors.lastname: Chlumská
authors.forename: P
authors.initials: P
authors.lastname: Lohse
mesh_terms: D000328:Adult; D015217:Cholesterol Ester Storage Disease / Q000175:diagnosis / Q000453:epidemiology; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D008049:Lipase / Q000172:deficiency*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015223:Wolman Disease / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D008049:Lipase