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Biochemical and Genetic Data from the Largest Global Fabry Cohort Reported to Present

Gabriela-Elena Oprea, PhD Sabrina Eichler, PhD Dr. rer. nat. Claudia Cozma, MD Tobias Boettcher Sabine Schröder Marius-Ionuț Iurașcu Jan Lukas, PhD Prof. Arndt Rolfs, MD
September 21, 2017

These findings were presented at the 13th International Congress Inborn Errors of Metabolism (ICIEM 2017).


Introduction:

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.

Summary:

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%).