BACKGROUND: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked, inherited genetic disease caused by a functional deficiency of lysosomal α-galactosidase, leading to the accumulation of glycosphingolipids in virtually all of the body's cell types and fluids. Patients with rare genetic diseases and non-specific symptoms often experience substantial diagnostic delays, which can negatively impact the prompt initiation of treatment. If FD is not treated specifically, end organ damage (such as chronic renal failure, hypertrophic cardiomyopathy with arrhythmia, and strokes) impairs quality of life and reduces life expectancy. PATIENTS AND METHODS: For 83 consecutive patients with FD referred to the Russian reference center for lysosomal storage diseases, family trees were built and genetic testing (cascade genotyping) was offered to family members. RESULTS: The pathogenic GLA variant associated with FD was identified for all 83 probands. Family testing using cascade genotyping enabled the identification of 165 additional cases of FD among the tested 331 at-risk family members. DISCUSSION: This is the first study to have described family screening in a large Russian cohort of patients with FD and chronic kidney disease. Raising awareness of FD among clinicians is important for earlier diagnosis and specific treatment.

2nd Department of Internal Medicine 1st Faculty of Medicine Charles University 12808 Prague Czech Republic

Division of Medical Genetics University of Versailles 78180 Montigny France

Faculty of Medicine Lomonosov Moscow State University 119991 Moscow Russia

Faculty of Medicine University of Puthisastra Phnom Penh 12211 Cambodia

Geneo Referral Centre for Fabry Disease Filière G2M MetabERN European Reference Network Paris Saclay University 92380 Garches France

Tareev Clinic of Internal Disease Sechenov 1st Moscow State Medical University 119991 Moscow Russia

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