Acid (Lysosomal) Lipase Deficiency. Overview of Czech Patients
Elleder M., Poupětová H., Ledvinová J.,
1
Hyánek J.,
2
Zeman J.,
3
Sýkora J.,
3
Stožický F.,
4
Chlumská A.,
5
Lohse P.
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Summary:
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 G 934 A 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: 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 frame
and to premature stop of the codon.
Key words:
acid lysosomal lipase, cholesterol ester storage, CESD, Wolman’s disease, subclinical course.
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