Lysosome acid lipase deficiency in Russian patients: molecular characteristic and epydemiology

Background. Lysosomal acid lipase deficiency (LALD) is a continuum of autosomal recessive diseases caused by defects in the enzyme of lipid metabolism, lysosomal acid lipase (LAL). LAL encodes by the gene LIPA. The most common variant of LIPA c.894G>A caused the disease in more than а half of cases. The true frequency of LALD is unknown. In Russia it is supposed to be 1:150000 - 1:100000 of newborns. The aim of the work is the selective biochemical screening for LALD, the study of LIPA mutation spectrum and the estimation of the LALD incidence in Moscow. Materials and methods. 1999 рatients suspected of lysosomal storage diseases (LSD) took part in the study. Dried blood spots of 920 newborns of Moscow were obtained for the estimation of c.894G>A allelic frequency. LAL activity was measured by fluorometric analysis. The LIPA gene was studied by direct sequencing and RFLP-analysis. Results and discussion. In 34 cases diagnosis of LALD was confirmed. Totally, 16 different variants of LIPA were found, 11 variants were novel. Ten of the novel variants were classified as pathogenic, one was uncertain significance. The allele c.894G>A was the most common LIPA variant in the cohort of patients, so as in many Europe populations. The allelic frequency of the variant in the newborns collection was estimated as 1:270 and LALD frequence was 1:73.159. Conclusion. Screening for LALD is a useful tool for diagnostics among LSD suspected patients. The allelic frequency of the variant c.894G>A seems the same as in European populations. In comparison with this data, there are many rare and novel variants in the Russian cohort.

кислая липаза, дефицит лизосомной кислой липазы, болезнь Вольмана, LIPA, лизосомные болезни накопления, ПДРФ-анализ, acid lipase, lysosomal acid lipase deficiency, Wolman disease, LIPA, lysosomal storage diseases, RFLP-analysis