Clinical and molecular findings in 44 Turkish patients with infantile-onset Pompe disease

Year 2025, Volume: 50 Issue: 3, 840 - 848, 30.09.2025

Deniz Kor , Caner Hacıoğlu , Fatma Derya Bulut , İrem Kaplan , Nazmiye Tüzel Gündüz , Ezgi Burgaç , Burcu Köşeci , Esra Kara , Sevcan Tuğ Bozdoğan , H. Neslihan Önenli Mungan

https://doi.org/10.17826/cumj.1710811

Abstract

Purpose: This study aims to investigate genotype–phenotype correlations in a cohort of 44 patients diagnosed with Infantile-onset Pompe disease (IOPD)
Materials and Methods: This retrospective study analyzed the clinical and genetic characteristics of 44 Turkish infants diagnosed with IOPD between 2009 and 2025. Data on clinical presentation, GAA mutations, treatment, and outcomes were collected and evaluated.
Results: The majority of patients (95.5%) presented with the classic IOPD phenotype. The mean age at symptom onset was 59.1 days, with cardiomegaly being the most common initial symptom. ERT was initiated at a mean age of 114.9 days. Despite treatment, the mortality rate remained high at 56.8%, with respiratory failure being the leading cause of death. All surviving patients exhibited improvement in cardiomyopathy; however, complications such as muscle weakness, kyphoscoliosis, and oropharyngeal dysfunction persisted. A total of 18 distinct GAA mutations were identified, including four novel variants. The most frequent mutation was p. L299P (42.9%). No definitive genotype–phenotype correlation was observed.
Conclusion: These findings highlight the genetic heterogeneity and clinical complexity of IOPD in a highly consanguineous population. The high prevalence of the p.L299P mutation suggests that it may represent a founder mutation in the Turkish population..

Keywords

Infantile-onset Pompe disease (IOPD) , Enzyme replacement therapy (ERT) , Genotype-phenotype correlation

Project Number

155/16.05.2025

İnfantil başlangıçlı Pompe hastalığı olan 44 Türk hastada klinik ve moleküler bulgular

Abstract

Amaç: Bu çalışma, infantil başlangıçlı Pompe hastalığı (IOPD) tanısı konmuş 44 hastadan oluşan bir kohortta genotip-fenotip korelasyonlarını araştırmayı amaçlamaktadır.
Gereç ve Yöntem: Bu retrospektif çalışmada, 2009 ile 2025 yılları arasında IOPD tanısı alan 44 Türk bebekte klinik ve genetik özellikler değerlendirilmiştir. Klinik bulgular, GAA mutasyonları, tedavi süreçleri ve sonuçlara ilişkin veriler analiz edilmiştir.
Bulgular: Hastaların büyük çoğunluğu (%95,5) klasik IOPD fenotipi göstermiştir. Semptomların ortalama başlangıç yaşı 59,1 gündür ve en sık ilk belirti kardiyomegali olmuştur. ERT ortalama 114,9 günlükken başlatılmıştır. Tedaviye rağmen mortalite oranı %56,8 olarak bulunmuş, en sık ölüm nedeni solunum yetmezliği olmuştur. Hayatta kalan tüm hastalarda kardiyomiyopatide düzelme gözlenmiş, ancak kas güçsüzlüğü, kifoskolyoz ve orofaringeal disfonksiyon gibi komplikasyonlar devam etmiştir. Toplam 18 farklı GAA mutasyonu saptanmış, bunlardan dördü literatürde daha önce bildirilmemiştir. En sık rastlanan mutasyon, %42,9 oranıyla p. L299P olmuştur. Genotip-fenotip arasında belirgin bir korelasyon saptanmamıştır.
Sonuç: Bulgularımız, yüksek oranda akraba evliliği görülen bir popülasyonda IOPD'nin genetik çeşitliliğini ve klinik karmaşıklığını vurgulamaktadır. p.L299P mutasyonunun yüksek sıklığı, bunun Türk toplumuna özgü bir kurucu (founder) mutasyon olabileceğini düşündürmektedir.

Keywords

İnfantil başlangıçlı Pompe Hastalığı , Enzim replasman tedavisi , genotip-fenotip koreasyonu

Project Number

155/16.05.2025

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