Clinical features, genetic analysis, and efficacy evaluation of hematopoietic stem cell transplantation in a case of osteopetrosis caused by compound heterozygous variations in the TNFRSF11A gene: a case study.

Osteopetrosis is an uncommon inherited skeletal condition arising from impaired osteoclast activity, with its autosomal recessive forms being linked to mutations in the TNFRSF11A gene. This study reports on a three-year-old Chinese girl presenting with recurrent fractures, short stature, and macrocephaly. Radiological examinations revealed diffusely elevated bone mineral density and constricted medullary spaces. Meanwhile, whole-exome sequencing detected compound heterozygous alterations in the TNFRSF11A gene: c.1567?+?2T>A inherited from the father and c.630C>G from the mother. The child underwent haploidentical hematopoietic stem cell transplantation (HSCT) from the father. Post-transplant follow-up showed improved growth (height/weight), resolved anemia, and alleviated optic foramen stenosis. The patient remained free of hepatosplenomegaly. This case report suggests that HSCT holds therapeutic potential for TNFRSF11A-related osteopetrosis and highlights the clinical value of early genetic diagnosis and timely transplantation for optimizing patient prognosis. Larger studies are required to confirm these findings and further guide the clinical management of similar rare disease cases.