DEFICIT KYSELÉ (LYSOZOMÁLNÍ) LIPÁZYPŘEHLED ČESKÝCH PACIENTŮ

Acid (Lysosomal) Lipase Deficiency. Overview of Czech Patients

Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage oftriacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediatedLDL 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 countryonly once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterizedby the storage of CE (which gave this entity the name of cholesteryl storage disease - CESD). Its main sign is affectionof the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotictransformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increasedVLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipidsis a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases ofCESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy withhepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patientswith permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quiteincidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis wasestablished in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) andmolecular genetic level (mutation in enzyme locus). In all instances mutation of G 934 A was found leading to reductionand loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations wereheterozygous. In one instance for technical reasons only one allele was analyzed. In three instances a point “missense”mutation was found: T 323 A (Trp 74 Arg), T4 75 A (Asp 124 Glu), A 210 T (Asp 36 Gl), in one instance a “nonsense” mutation:C 233 T (Arg 44 -stop) and twice a deletion mutation D C 673-5 and D G 1068-8 leading to impairment of the reading frameand to premature stop of the codon.

Key words:
acid lysosomal lipase, cholesterol ester storage, CESD, Wolman’s disease, subclinical course.