Berrak BİLGİNER GÜRBÜZ, Fatma Derya BULUT, Habibe KOÇ UÇAR, Esra SARIGEÇİLİ, Bilge SARIKEPE, Özge ÖZALP YÜREĞİR

GM2 gangliosidozis: üç yeni mutasyonlu hastaların klinik, biyokimyasal ve genetik bulgularının değerlendirilmesi

Amaç: Bu çalışmanın amacı, GM2 gangliosidozlu çocukların tanı özelliklerini, klinik bulgularını, fenotipik ve genotipik özelliklerini değerlendirmektir. Gereç ve Yöntem: Kliniğimizde GM2 gangliosidoz tanısı alan 14 hastanın dosya kayıtları retrospektif olarak incelendi. GM2 gangliosidoz tanısı; serum total heksosaminidaz ile β-heksosaminidaz aktivitesi düzeyleri ve genetik analiz ile doğrulandı. Bulgular: On dört hastada üçü novel (biri HEXA geninde ve ikisi HEXB geninde) olmak üzere toplam yedi farklı mutasyon saptandı. HEXA mutasyonu olan hastalarda c.1100_1111del (p.Gly367_Tyr370del) mutasyonu yüksek sıklıkta bulundu. Tay-Sachs (TSD) ve Sandhoff (SD) tanılı hastaların ortalama tanı yaşı sırasıyla 13,4±6,3 ay ve 14,2±4,2 aydı. Hastaların %92.9'unda nöroregresyon mevcuttu. On dört hastanın 11'inde epilepsi, 10'unda gelişim geriliği, 6'sında hiperakuzi, 6'sında cherry-red spot ve 6'sında makrosefali saptanırken, hiçbir hastada organomegali görülmedi. Sonuç: Gelişim geriliği ve/veya gecikmesi olan çocuklarda GM2 gangliosidoz hastalığı akla gelmelidir. GM2 gangliosidoz şüphesi olan çocuklarda klinik bulgular varlığında erken tanı için enzim analizi ve gen tespiti yapılmalıdır.

Anahtar Kelimeler:

Lizozomal depo hastalıkları, GM2 gangliosidoz, hekzosaminidaz, Tay-Sachs hastalığı; Sandhoff hastalığı

GM2 gangliosidoses: evaluation of clinical, biochemical and genetic findings of patients with three novel mutations

Purpose: The aim of this study is to evaluate the diagnosis characteristics, clinic findings, phenotypical and genotypical features of children with GM2 gangliosidoses. Materials and Methods: The file records of 14 patients diagnosed with GM2 gangliosidoses in our clinic were retrospectively reviewed. The GM2 gangliosidoses diagnosis was confirmed by determining the levels of serum total hexosaminidase and β-hexosaminidase activity with genetic analysis. Results: We identified a total of seven different mutations, three of which were novel (one in the HEXA gene and two in the HEXB gene) in 14 patients. We found a high frequency of c.1100_1111del (p.Gly367_Tyr370del) mutation in HEXA affected patients. The mean age at diagnosis was 13.46.3 months and 14.24.2 months for patients with Tay–Sachs disease (TSD) and Sandhoff disease (SD) respectively. Neuroregression was present in 92.9% of our patients. Of the 14 patients, 11 had epilepsy, 10 had developmental delay, 6 had hyperacusis, 6 had cherry-red spots and 6 had macrocephaly, but none of the patients had organomegaly. Conclusion: GM2 gangliosidoses disease should be considered for children with developmental regression and/or delay. For early diagnosis, enzyme analysis and gene detection should be performed in children with suspected GM2 gangliosidoses in the presence of clinical findings.

Keywords:

Lysosomal storage disorders GM2 gangliosidoses, hexosaminidase, Tay-Sachs disease, Sandhoff disease,

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