CLINICAL SPECTRUM AND THERAPEUTIC ADVANCES IN PEDIATRIC PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder driven by somatic PIGA mutations, leading to uncontrolled complement activation, intravascular hemolysis, and thrombotic risk. Pediatric PNH represents fewer than 10% of cases and demonstrates a distinct clinical phenotype that complicates diagnosis and management. Methods: A comprehensive literature search of PubMed, Embase, Web of Science, and Scopus was conducted through July 2025 using predefined keywords related to PNH, pediatrics, bone marrow failure, and complement inhibitors. Eligible studies included clinical trials, registry data, systematic reviews, case series, and case reports. Relevant adult studies were also reviewed when mechanistic or therapeutic insights were applicable to pediatric disease. Data were synthesized narratively, focusing on pathophysiology, clinical spectrum, diagnostic approaches, and therapeutic advances. Results: Pediatric PNH most often presents with bone marrow failure syndromes rather than classic hemolytic features. Hemoglobinuria is infrequent, while cytopenias predominate. Thrombosis, though less common than in adults, remains a serious complication. High-sensitivity flow cytometry enables early and accurate diagnosis, particularly for small clone sizes. Complement inhibitors—including eculizumab, ravulizumab, and crovalimab—have markedly improved survival and reduced morbidity, while emerging agents targeting proximal complement pathways (pegcetacoplan, iptacopan, danicopan) show promise. Hematopoietic cell transplantation remains the only curative option but is reserved for selected patients. Conclusions: Pediatric PNH differs significantly from adult disease in presentation and management. Advances in complement inhibition have transformed prognosis, but further pediatric-specific research and inclusion in clinical trials are urgently needed to establish evidence-based guidelines and optimize long-term outcomes.