Case Report: Neonatal ultra-severe hemolytic anemia complicated by pulmonary hypertension induced by compound heterozygous variants in the KLF1 gene and literature review

Objective To investigate the clinical characteristics, genotypic profiles, and diagnostic/therapeutic strategies for congenital hemolytic anemia induced by compound heterozygous variants in the KLF1 gene. Methods We retrospectively analyzed the clinical data of a neonate who presented primarily with ultra-severe anemia, elevated direct bilirubin, and pulmonary hypertension. Whole-exome sequencing (WES) was utilized for variant identification, followed by a comprehensive review of literature. Results The patient, a female neonate, developed severe anemia within 10 h of birth, accompanied by rapidly progressing hyperbilirubinemia (predominantly direct hyperbilirubinemia). Bedside echocardiography revealed a patent ductus arteriosus (PDA) and pulmonary hypertension. Trio-WES identified pathogenic compound heterozygous variants in the KLF1 gene: c.519_525dup (p.Gly176ArgfsTer179) and c.1012C > A (p.Pro338Thr). Following multiple red blood cell transfusions and mechanical ventilatory support, the infant's condition stabilized. During a 24-month follow-up, the patient exhibited transfusion-dependent anemia. Conclusion For neonates presenting with unexplained (Coombs/DAT-negative) severe hemolytic anemia, particularly when complicated by pulmonary hypertension and atypical cholestasis, early genetic testing should be performed to rule out KLF1 -related diseases.