Yüksek akrabalık oranına sahip bir bölgede yeni GLA mutasyonu: Türkiye'de Fabry hastalığı taramasından elde edilen bulgular

Abstract

Giriş: Fabry hastalığı (FH), α-galaktosidaz A (α-Gal A) enzim eksikliğine bağlı olarak gelişen X'e bağlı kalıtılan lizozomal depo hastalığıdır. Çoklu organ sistemlerinde globotriaosilseramidin birikimine neden olur. Erken tanı özellikle yüksek riskli popülasyonlarda hâlâ önemli bir zorluktur. Bu çalışmanın amacı, akraba evliliği oranının yüksek olduğu Doğu ve Güneydoğu Anadolu bölgelerinde hemodiyaliz hastalarında Fabry hastalığı prevalansını belirlemektir. Yöntem: 2015–2019 yılları arasında beş ilde düzenli hemodiyaliz tedavisi alan 613 erişkin hasta kuru kan örneği ile α-Gal A aktivitesi açısından tarandı. Enzim düzeyi düşük saptanan hastalarda lökosit enzim analizi ve GLA gen dizilemesi ile doğrulayıcı testler yapıldı. Bulgular: Hastaların %15,7’sinde α-Gal A aktivitesi düşük bulundu. Genetik analiz yapılan 58 bireyde erkeklerde mutasyon tespit edilmedi. Ancak, birbiriyle akraba olmayan iki kadın hastada daha önce gnomAD veya ClinVar veri tabanlarında bildirilmeyen aynı GLA gen varyantı c.116C>A (p.T39K) saptandı. Bu kohortta genetik olarak doğrulanmış FH prevalansı %0,32 olarak hesaplandı. Sonuç: Bu çalışma, Türkiye'nin Doğu ve Güneydoğu bölgelerinde gerçekleştirilen ilk bölgesel Fabry hastalığı tarama çalışmasıdır. Yüksek akrabalık oranına sahip bir popülasyonda yeni bir GLA mutasyonunun tespit edilmesi, hemodiyaliz hastalarında genetik taramanın önemini ve bölgeye özgü tanı ve genetik danışmanlık stratejilerine olan ihtiyacı vurgulamaktadır.

Keywords

• Fabry hastalığı
• Hemodiyaliz taraması
• GLA geni
• Akrabalık

Novel GLA mutation in a high-consanguinity region: insights from Fabry disease screening in Turkiye

Abstract

Aims: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient α-galactosidase A (α-Gal A) activity, leading to the accumulation of globotriaosylceramide in multiple organ systems. Its early diagnosis remains a challenge, particularly in high-risk populations. This study aimed to determine the prevalence of FD among hemodialysis patients in Eastern and Southeastern Turkiye, regions with a high rate of consanguineous marriages. Methods: Between 2015 and 2019, 613 adult patients undergoing maintenance hemodialysis across five provinces were screened for α-Gal A activity using dried blood spot testing. Patients with reduced enzyme levels underwent confirmatory testing through leukocyte enzyme assays and GLA gene sequencing. Results: Reduced α-Gal A activity was identified in 15.7% of patients. Genetic analysis in 58 individuals revealed no mutations in males. However, two unrelated female patients were found to carry the same GLA gene variant, c.116C>A (p.T39K), which has not been previously reported in gnomAD or ClinVar databases. The overall prevalence of genetically confirmed FD in this cohort was 0.32%. Conclusion: This is the first regional screening study of FD in Eastern and Southeastern Turkiye. The identification of a novel GLA mutation in a high-consanguinity population underscores the importance of genetic screening in dialysis patients and highlights the need for region-specific diagnostic and counseling strategies.

Keywords

• Fabry disease
• hemodialysis screening
• GLA gene
• consanguinity

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