Biochemical and genetic data from the largest global Fabry cohort reported to present
These findings were presented at the 13th International Congress Inborn Errors of Metabolism (ICIEM 2017).
Fabry disease is an X-linked inherited lysosomal storage disease characterized by a deficient alpha-galactosidase caused by mutations in GLA gene. We present here the data collected over a period of over10 years regarding in vitro Fabry diagnosis.
Material and methods:
Fabry diagnosis is performed in a high-throughput stepwise manner: (a.) males- enzymatic activity, lyso-Gb3 quantification, followed by GLA gene sequencing and, (b.) females- GLA gene sequencing followed by lyso-Gb3. Enzymatic activity was determined in dried blood spots using either MS detection or mass spectrometric detection of the enzymatic product. Lyso-Gb3 was measured using mass spectrometry (LC/MRM-MS). The biochemical diagnosis was confirmed in all cases by genetic analysis. GLA gene sequencing was performed using single gene analysis, MLPA or NGS panel sequencing.
We report the identification of over 390 unique GLA genetic variants in over 3,330 different individuals. From the 3,641 pathogenic alleles sequenced in this study, the most abundant were: c. 937G>T (18.3%); c. 352A>G (9.8%); c. 376C>T (6.2%); c. 427G>A (3.4%).