The role of globotriaosylsphingosine in the diagnosis of Fabry disease in Russian patients

Fabry Disease (BF), MIM 301500 - X-linked disease caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase A (α-gal A). In 2017, a method for determining the concentration of lyso-Gb3 for the diagnosis of FD was developed and introduced in the laboratory of molecular genetics and medical genomics of the “National Medical Research of Children’s Health Federal State Autonomous Institution of the Ministry of Health of the Russian Federation. To date, we have studied 9830 samples of dry blood spots from various regions of Russia, obtained from 8832 male and 998 female patients, aged 12 to 70 years. As a result of the study, a decrease in enzyme activity was detected in 33 men, and in 31 of them an increase in the concentration of lyso-Gb3, pathogenic variants of the GLA gene were found in these men, while the two remaining men found polymorphic variants of the GLA gene, previously described as alleles with pseudodeficiency activity. In addition, 2 women with an increased concentration of lyso-Gb3 were identified, in whom pathogenic variants of the GLA gene were also detected, while in 5 women with pseudo-deficient alleles of the GLA gene, the concentration of lyso-Gb3 was normal. Our study demonstrated the advantage of measuring the concentration of the lyso-Gb3 biomarker compared to determining the activity of the α-gal A enzyme for the initial diagnosis of men with suspected FD, as well as the possibility of using this biomarker for the initial diagnosis of women with suspected DF.

Fabry disease, α-galactosidase A, glycosphingolipid, globotriaosylsphingosine, lysosomal storage disease, tandem mass-spectrometry, sequencing, mutations of the GLA gene