Çocukluk Çağında Benign Trombositopeni ve Yeni TURBB1, ANKRD26 ve SAMD9 Varyantları

Amaç: Trombositopeni çocuklarda sık görülen bir hematolojik bulgudur. Bu çalışmada trombositopenili çocukların demografik, laboratuvar, genetik özelliklerinin ve prognozlarının değerlendirilmesi amaçlandı. Gereç ve Yöntem: Bu retrospektif çalışmaya Aralık 2021-Ağustos 2023 tarihleri arasında Düzce Üniversitesi Tıp Fakültesi Çocuk Hematoloji-Onkoloji Polikliniği’nde trombositopeni tanısı konulan çocuklar (n=82) dahil edildi. İdiyopatik trombositopenik purpurası (n=41) olan ve olmayan (n=41) trombositopenili olguların laboratuvar, klinik, ve tedavileri karşılaştırıldı. Seçilmiş olgularda klinik ekzom yeni nesil sekanslama ile gen analizi yapıldı. Bulgular: İmmun trombositopenik purpura (İTP)’li olmayan çocuklarda (n=41) İTP’lilere göre (n=41) ateş (p<0,001), enfeksiyon (p<0,001), bisitopeni veya pansitopeni (p=0,013) ve solukluk (p=0,014) oranları daha yüksekti. İTP’li hastalarda, İTP’li olmayan hastalara göre trombosit sayısının ortanca değeri (p<0,001) anlamlı olarak daha düşük ve ortalama nötrofil düzeyleri (±SD) (p=0,003) daha yüksekti. Enfeksiyonu olan çocuklarda (n=22), enfeksiyonu olmayanlara (n=60) göre yüksek ateş (p<0,001), solukluk (p<0,001), bisitopeni ve pansitopeni (p=0,04) daha sık ve ortalama trombosit düzeyleri (± SD) ile nötrofil düzeyleri (p=0,004) daha düşük bulundu. Ortanca trombositopeni süresi (15 güne karşın 90 gün) (p=0,04) enfekte grupta daha kısaydı. Hafif makrotrombositopenisi olan bir erkek çocukta klinik ekzom yeni nesil sekanslama analizinde üç yeni variant tanımlandı. ANKRD26 geninde 3:c. 340A >G (p. Arg114Gly) varyantı, SAMD9 geninde 002G>A (p. Asp668Asn) varyantı ve TUBB1 geninde 1342 G>T (p. Asp448Tyr) varyantı saptandı. Yeni TUBB1 varyantı hastanın kliniği ile uyumlu bulundu. Sonuç: Enfeksiyona bağlı trombositopeni, İTP’ye göre daha yüksek trombosit sayıları ile daha hızlı iyileşir. Konjenital makrotrombositopeni tanısı için atipik İTP’li olgularda klinik ekzom yeni nesil sekanslama analizi önerilir.

Anahtar Kelimeler:

ÇOCUK, İdiyopatik trombositopenik purpura, moleküler genetik, trombositopeni

Benign Thrombocytopenia in Childhood and Novel TURBB1, ANKRD26, and SAMD9 Variants

Aim: Thrombocytopenia is a common hematologic finding in children. This study evaluated the demographic, laboratory and genetic characteristics and prognosis of children with thrombocytopenia. Material and Method: This retrospective study included children (n=82) examined with thrombocytopenia at Düzce University Faculty of Medicine Pediatric Hematology-Oncology Clinic between December 2021 and August 2023. Laboratory, clinical, and treatment characteristics of patients with idiopathic thrombocytopenic purpura (n=41) and without thrombocytopenia (n=41) were compared. Gene analysis was performed by clinical exome next-generation sequencing in selected cases. Results: Children without idiopathic thrombocytopenic purpura (ITP) (n=41) had higher rates of fever (p<0.001), infection (p<0.001), cytopenia or pancytopenia (p=0.013) and pallor (p=0.014) than children with ITP (n=41). The median platelet count was significantly lower (p<0.001) and neutrophil levels (mean ± SD) (p=0.003) were higher in patients with ITP compared to patients without ITP. In children with infection (n=22), high fever (p<0.001), pallor (p<0.001), cytopenia and pancytopenia (p=0.04) were more frequent and mean platelet levels (± SD) and neutrophil levels (p=0. 004) were lower than those without infection (n=60). The median duration of thrombocytopenia (15 days vs. 90 days) (p=0. 04) was shorter in the infected group. Three novel variants were identified by clinical exome next-generation sequencing analysis in a boy with mild macrothrombocytopaenia. Three novel variants in one patient in the genes; a three :c. 340A >G (p. Arg114Gly) variant, a 002G>A (p. Asp668Asn) variant in the ANKRD26 gene in the SAMD9 gene and in the TUBB1 gene a 1342 G>T (p. Asp448Tyr) variant. The new TUBB1 variant was consistent with the patient’s clinical presentation. Conclusion: Infection-associated thrombocytopenia improves faster with higher platelet counts than ITP. Clinical exome next-generation sequencing analysis is recommended in cases with atypical ITP to diagnose congenital macrothrombocytopaenia.

Keywords:

Idiopathic thrombocytopenic purpura, molecular genetics, thrombocytopenia, child,

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