Rashid Anila, Mushtaq Naureen, Mansoori Huma
Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK.
Department of Oncology, Aga Khan University Hospital, Karachi, PAK.
Cureus. 2020 Dec 13;12(12):e12053. doi: 10.7759/cureus.12053.
Congenital thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and thrombosis. Congenital TTP should also be considered while investigating neonatal hyperbilirubinemia, hemolytic anemia, or isolated thrombocytopenia. This case is of an 8-year-old male child who presented with prolonged and recurrent history of thrombocytopenia and MAHA, first identified when he was seven weeks of age preceding neonatal hyperbilirubinemia. Peripheral blood smear examination showed thrombocytopenia and schistocytes. He then went through a series of laboratory investigations until at the age of seven years, when the ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) antigen level was performed and found to be low: 40 ng/ml (630-850). Subsequently, he received a trial of steroids and rituximab which were found to be ineffective and associated with complications. In this case, a definitive diagnosis was delayed until the age of eight years when a novel homozygous pathogenic frameshift variant ADAMTS13 c.3033delC, p.Cys1012AlafsX109 in exon 23 was identified. After receiving regular plasma infusions, thrombocytopenia and hemolysis improved. Congenital TTP should be considered in every neonatal hyperbilirubinemia, thrombocytopenia or hemolytic anemia to avoid delay in diagnosis. Early diagnosis through analysis of the ADAMTS13 gene is crucial for optimal management as well as for genetic counselling.
先天性血栓性血小板减少性紫癜(TTP)是一种常染色体隐性疾病,其特征为血小板减少、微血管病性溶血性贫血(MAHA)和血栓形成。在调查新生儿高胆红素血症、溶血性贫血或孤立性血小板减少症时,也应考虑先天性TTP。本病例为一名8岁男童,有长期反复的血小板减少和MAHA病史,首次发现于其7周龄时,当时伴有新生儿高胆红素血症。外周血涂片检查显示血小板减少和裂红细胞。随后,他接受了一系列实验室检查,直到7岁时检测了ADAMTS13(含血小板反应蛋白1型基序的解整合素和金属蛋白酶13)抗原水平,发现其较低:40 ng/ml(630 - 850)。随后,他接受了类固醇和利妥昔单抗试验,但发现无效且伴有并发症。在本病例中,直到8岁时才确诊,当时在外显子23中发现了一种新的纯合致病性移码变异ADAMTS13 c.3033delC,p.Cys1012AlafsX109。接受定期血浆输注后,血小板减少和溶血情况有所改善。对于每一例新生儿高胆红素血症、血小板减少症或溶血性贫血,都应考虑先天性TTP,以避免诊断延误。通过分析ADAMTS13基因进行早期诊断对于优化治疗以及遗传咨询至关重要。