Malignant Infantile Osteopetrosis: A Rare Cause of Refractory Thrombocytopenia

Background: Infantile Malignant Osteopetrosis (IMO) is a rare autosomal recessive bone disorder characterized by defective osteoclastic bone resorption, leading to excessive bone density and marrow failure. While rare (1 in 250,000 live births), it is a life-threatening condition that requires early identification to prevent irreversible neurological damage and mortality.

Case Presentation: A 25-day-old term male infant, born to third-degree consanguineous parents, presented for evaluation of an abnormal newborn screen (elevated 17-OH progesterone) and a facial rash. Clinical examination revealed significant splenomegaly (5 cm below the costal margin) and severe refractory thrombocytopenia (27,000 cells/cu.mm). Initial management for suspected sepsis, alloimmune thrombocytopenia, and TORCH infections was unsuccessful, with platelet counts remaining refractory to IV immunoglobulin and transfusions. A subsequent skeletal survey revealed diffuse skeletal sclerosis and pathognomonic "bone-within-bone" appearances in the long bones. Ophthalmic evaluation confirmed pale discs and foveal atrophy. Whole Exome Sequencing identified a likely pathogenic homozygous variant in the CLCN7 gene. Despite counseling on the necessity of hematopoietic stem cell transplantation (HSCT), the parents opted for conservative management due to the poor prognosis associated with this genetic variant.

Discussion: This case highlights IMO as a critical differential diagnosis for neonatal refractory thrombocytopenia and splenomegaly. The progressive obliteration of the medullary cavity leads to bone marrow insufficiency and compensatory extramedullary hematopoiesis. Early diagnosis is vital, as HSCT remains the only curative treatment; however, variants in genes like CLCN7 can involve primary CNS pathology, complicating the clinical outlook.

Conclusion: Clinicians should maintain a high index of suspicion for osteopetrosis in neonates with unexplained bicytopenia and organomegaly. Rapid radiographic screening and genetic testing are essential for timely intervention and informed genetic counseling for affected families