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

Year 2023, Volume: 1 Issue: 3, 85 - 91, 31.10.2023

Hatice Mine Çakmak , Yaşar Bildirici

Abstract

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.

Keywords

ÇOCUK, İdiyopatik trombositopenik purpura, moleküler genetik, trombositopeni

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

Abstract

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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