Ayça KIYKIM, Işıl BARLAN, Elif AYDINER KARAKOÇ, Havva Hasret ÇAĞAN, Kaan BOZTUG, Safa BARIŞ

Doğuştan ağır nötropenide fenotip-genotip ilişkisi

Amaç: Doğuştan ağır nötropeni, yaşamın erken döneminde sepsis, apse, omfalit, diş eti iltihabı gibi enfeksiyon bulgularıyla karşımıza çıkan nadir görülen kalıtsal bir hastalıktır. Çalışmamızda genetik tanısı konulan hastalarımızın mutasyonları ile klinik bulguları arasındaki ilişkiyi değerlendirdik. Gereç ve Yöntem: Kliniğimizde takip edilen toplam altı hastanın klinik, laboratuvar ve tedavi verileri elde edilerek hem hastalara, hem de diğer aile bireylerine (ebeveynler ve çocuklar) mutasyon analizi yapıldı. Bulgular: Doğuştan ağır nötropeni nedeniyle izlenen altı olgunun erken dönemde en sık apse, otit ve diş eti iltihabı nedeniyle başvurduğu gözlendi. Dört olguda HAX-1, iki olguda G6PC3 mutasyonu saptandı. Glükoz-6-fosfataz katalitik alt birim 3 mutasyonu olan olgularda yüzeyel deri venlerinde belirginleşme, meme başı çöküklüğü, üçgen yüz görünümü vardı. HS1-ilişkili protein X-1 mutasyonu saptanan olgularda gelişme geriliği, konuşamama, konvulziyon ve öğrenme güçlüğü gözlendi. Çıkarımlar: Tekrarlayıcı, ağır enfeksiyon öyküsü olan olgularda öncelikle nötrofil sayısına dikkat edilmesi, değişik klinik bulgularla başvuranlarda erken tanı ve tedavi açısından gen analizinin yanı sıra genetik danışmanın yapılması önemlidir.

The phenotype-genotype relationship in severe congenital neutropenia patients

Aim: Severe congenital neutropenia is a rare hereditary disease presenting with infections such as sepsis, abscess, omphalitis and gingivitis in early life. We evaluated the association between clinical findings and mutations in our patients with severe congenital neutropenia. Material and Method: The clinical and laboratory findings of six patients with severe congenital neutropenia were obtained and the diagnosis was confirmed by mutation analysis in all family members (parents and children). Results: The most common clinical presentation included formation of abscess and presence of otitis and gingivitis. The mutation analysis by DNA sequencing revealed HAX-1 mutation in four and G6PC3 mutation in two patients. Prominent superficial veins, inverted nipple and triangular face were observed in patients with G6PC3 mutation. In addition, developmental delay, convulsion, inability to speak and learning difficulties were observed in two patients with HAX1 mutation. Conclusions: In patients with severe, recurrent infections, assessment of neutrophil count and consideration of various presentations of severe congenital neutropenia are critical for establishing early diagnosis and for successful treatment of the disease. Additionally, genetic counseling and mutation analysis should be offered to these patients.

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