Molybdenum Cofactor Deficiency – A Single-Center Experience

Öz

Objective: Molybdenum cofactor deficiency (MoCD) is a rare, severe, autosomal recessive metabolic disorder characterized by the loss of function of molybdenum-dependent enzymes. This study aimed to evaluate the clinical, biochemical, radiological, and genetic features of MoCD patients followed in our center. Material and Methods: Medical records of 10 patients diagnosed with MoCD at the Hacettepe University Department of Pediatric Metabolism between 2009 and 2025 were retrospectively reviewed. Demographic characteristics, clinical findings, laboratory results, neuroimaging and EEG findings, and genetic analyses were assessed. Results: Eight patients were male (n=8), and parental consanguinity was present in nine patients (n=9). Eight patients were classified as early-onset, while two were late-onset. Seizures were the most common presenting symptom in early-onset patients, whereas late-onset cases presented with post-infectious motor deficits without seizures. Laboratory evaluation revealed universally low plasma uric acid levels (0-2 mg/dL) and variable urinary sulfite levels. Neuroimaging showed cystic encephalomalacia in all patients. Neuroimaging showed cystic encephalomalacia in all patients. Genetic analysis, performed in seven patients, identified MOCS1 variants in three patients and MOCS2 variants in four patients. During follow-up, seven patients died, with ages at death ranging from 6 to 103 months. Six of the seven deceased patients belonged to the early-onset MoCD group. Three patients are still alive. The mean survival time was 73.4 months. Conclusion: MoCD should be considered in the differential diagnosis of neonates presenting with intractable seizures and low uric acid levels, but clinicians should also be aware that clinical manifestations may appear beyond the neonatal period.

Anahtar Kelimeler

• Early-onset
• late-onset
• molybdenum cofactor deficiency
• sulfur
• uric acid

MOLİBDEN KOFAKTÖR EKSİKLİĞİ-TEK MERKEZ DENEYİMİ

Öz

Amaç: Molibden kofaktör eksikliği (MoKE), molibden-bağımlı enzimlerin işlev kaybı ile karakterize, nadir görülen, ağır seyirli otozomal resesif geçişli bir metabolik hastalıktır. Bu çalışmada bölümümüzde takip edilen MoKE olgularının klinik, biyokimyasal, radyolojik ve genetik özelliklerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Hacettepe Üniversitesi Çocuk Metabolizma Bilim Dalında 2009-2025 yılları arasında MoKE tanısı alan 10 hastanın dosyaları geriye dönük olarak incelendi. Bulgular: Hastaların demografik özellikleri, klinik bulguları, laboratuvar sonuçları, görüntüleme ve EEG bulguları ile genetik analizleri değerlendirildi. Olguların 8’i erkekti (n=8) ve 9’unda (n=9) ebeveynler arasında akrabalık vardı. Sekiz hasta erken, iki hasta geç başlangıçlı MoKE grubundaydı. Erken başlangıçlı olgularda nöbetler en sık bulgu iken geç başlangıçlı olgular enfeksiyon sonrası gelişen motor kayıp ile başvurmuş ve nöbet izlenmemiştir. Laboratuvar incelemelerinde tüm hastalarda ürik asit düzeyi düşük olup 0-2 mg/dL aralığındaydı ve idrar sülfit düzeyleri değişkendi. Kraniyal görüntülemede tüm olgularda kistik ensefalomalazi saptanmıştır. Genetik analiz yapılan 7 hastadan 3’ünde MOCS1, 4’ünde MOCS2 varyantı gösterilmiştir. İzlemde 7 hasta kaybedilmiş olup kaybedilme yaşları 6-103 ay arasındaydı. Kaybedilen 7 hastanın 6’sı erken başlangıçlı MoKE grubundaydı. 3 hasta yaşamını sürdürmektedir. Ortalama yaşam süresi 73,4 aydır. Sonuç: MoKE yenidoğan döneminde başlayan inatçı nöbet ve düşük ürik asit düzeyi varlığında ayırıcı tanıda ön planda düşünülmelidir. Yenidoğan dönemi dışında da klinik bulguların görülebileceği unutulmamalıdır.

Anahtar Kelimeler

• Erken başlangıç
• geç başlangıç
• molibden kofaktör eksikliği
• sülfür
• ürik asit

Kaynakça

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