AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by α-galactosidase A (AGALA) deficiency. Whereas 'classic' variant has multisystemic manifestation, the more recently described 'later-onset' variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso-Gb3 ) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity <1.2 μmol/h/L and in females with either low AGALA activity or lyso-Gb3 > 3.5 ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1 ± 4.3 mm). The average age was 58.4 ± 14.7 years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later-onset cardiac FD. CONCLUSIONS: We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non-selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.

• Klíčová slova
• Alpha-galactosidase, Fabry disease, Genetic testing, Hypertrophic cardiomyopathy, Lyso-Gb3, Screening,
• MeSH
• alfa-galaktosidasa genetika   MeSH
• dospělí MeSH
• Fabryho nemoc * diagnóza   epidemiologie   genetika   MeSH
• genetické testování MeSH
• hypertrofická kardiomyopatie * diagnóza   epidemiologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• alfa-galaktosidasa MeSH

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.

• Klíčová slova
• Fabry disease, cascade genotyping, early diagnosis, family screening, rare diseases,
• MeSH
• alfa-galaktosidasa genetika   MeSH
• chronická renální insuficience * diagnóza   genetika   MeSH
• Fabryho nemoc * diagnóza   genetika   metabolismus   MeSH
• genetické testování MeSH
• glykosfingolipidy MeSH
• kvalita života MeSH
• lidé MeSH
• mutace MeSH
• rodina MeSH
• vzácné nemoci genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-galaktosidasa MeSH
• glykosfingolipidy MeSH