Biyotinidaz Eksikliği Şüphesiyle Başvuran Hastaların Klinik Bulguları ve BTD Geni Moleküler Analizi Sonuçları

Abstract

Amaç: Biyotinidaz eksikliği, biyotinidaz üretiminden sorumlu biyotinidaz (BTD) genindeki patojenik mutasyonların neden olduğu, geç başlangıçlı biyotine duyarlı multipl karboksilaz eksikliği olarak da bilinen otozomal resesif geçişli bir hastalıktır. Bu çalışmada biyotinidaz eksikliği nedeniyle başvuran hastaların klinik bulgularının ve BTD geni moleküler analizi sonuçlarının literatür eşliğinde sunulması amaçlanmıştır.

Gereç ve Yöntemler: Topuk kanı taramasında pozitif olan, nörolojik, duyusal, solunum ve cilt bulguları biyotinidaz eksikliği ile uyumlu olan 9 hasta çalışmaya dahil edilmiştir. Çalışmaya dahil edilen olgulardan genomik DNA izolasyonu için 2 cc periferik kan Etilen Diamin Tetra Asetik Asitli (EDTA) tüplere alınmış ve genomik DNA’ları izole edilerek BTD geninin dizi analizi yapılmıştır.

Bulgular: Yapılan BTD geni tüm ekzon dizi analizi sonuçlarına göre 1 hastada homozigot c.1368A>C/p.Gln456His mutasyonu, 1 hastada heterozigot c.1368A>C/p.Gln456His mutasyonu, 1 hastada birleşik heterozigot c.1330G>C/p.Asp444His ve c.511G>A/p.Ala171Thr mutasyonu, 1 hastada birleşik heterozigot c.1336G>C/p.Asp446His ve c.511G>A/p.Ala171Thr mutasyonu, 1 hastada ise heterozigot c.557G>A/p.Cys186Tyr mutasyonu tespit edildi. Dört hastada herhangi bir mutasyon tespit edilmedi.

Sonuç: BTD bozukluğu olan hastaların yaşadığı sıkıntıların giderilebilmesi ve gecikme halinde ortaya çıkabilecek komplikasyonların önlenmesi için erken tanı ve tedavi oldukça önemlidir. Hastaya ve aile bireylerine genetik danışmanlık verilerek otozomal resesif kalıtılan hastalık için prenatal tanı veya preimplantasyon genetik tanı yöntemi şansının mevcut olduğu hakkında bilgilendirme yapılması, taşıyıcı ailelerin sağlıklı çocuk sahibi olması açısından önemlidir.

Keywords

• Biyotinidaz eksikliği,BTD geni,geç başlangıçlı biyotine duyarlı multipl karboksilaz eksikliği

Clinical Findings and BTD Gene Molecular Analysis Results of Patients Presenting with Suspicion of Biotinidase Deficiency

Abstract

Aim: Biotinidase deficiency is an autosomal recessive disease, also known as late-onset biotin-sensitive multiple carboxylase deficiency caused by pathogenic mutations in the biotinidase (BTD) gene responsible for the production of biotinidase. In this study, we aimed to present the clinical findings and BTD gene molecular analysis results in the light of the literature.

Material and Methods: Nine patients who were positive in heel blood screening and cases compatible with neurological, sensory, metabolic, respiration and skin findings of biotinidase deficiency were included in the study. For the isolation of genomic DNA from the participants included in the study, 2 cc of peripheral blood was taken into Ethylene Diamine Tetra Acetic Acid (EDTA) tubes and their genomic DNA was isolated and sequence analysis of the BTD gene was performed.

Results: According to the all exon sequence analysis results of the BTD gene, homozygous c.1368A>C/p.Gln456His mutation was detected in 1 patient; heterozygous c.1368A>C/p.Gln456His mutation was detected in 1 patient; combined heterozygous c.1330G>C/p.Asp444His and c.511G>A/p.Ala171Thr mutations were detected in 1 patient, combined heterozygous c.1336G>C/p.Asp446His and c.511G>A/p.Ala171Thr were detected in 1 patient, and c.557G>A/p.Cys186Tyr mutation was detected in 1 patient. No mutation was detected in 4 patients.

Conclusion: Early diagnosis and treatment are very important for eliminating the problems experienced by patients with BTD disorder and for preventing complications that may occur in case of delay. It is important that informing the patient and family members about the prenatal diagnosis or preimplantation genetic diagnosis method for autosomal recessive inherited disease by giving genetic counseling.

Keywords

• Biotinidase deficiency,BTD gene,late-onset biotine sensitive multiple carboxylase deficiency

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