Osteopetrose

Osteopetrose, also known as osteopetrosis or marble bone disease, is a rare inherited disorder characterized by abnormally dense bones resulting from defective osteoclast-mediated bone resorption. Although bone mass is increased, the bones are brittle and prone to fracture, and the marrow spaces are reduced, leading to hematologic and immunologic complications.

Genetics and pathophysiology: The severe infantile malignant form is usually autosomal recessive and is commonly linked to mutations in genes such as TCIRG1 and CLCN7, among others. Autosomal dominant, milder forms also exist and are associated with mutations in CLCN7 and other osteoclast-related genes. The primary defect impairs acidification of the resorption lacuna, hindering normal bone remodeling and causing diffuse skeletal sclerosis with narrowed or absent medullary cavities.

Clinical features: Infantile forms typically present in early life with anemia, thrombocytopenia, and hepatosplenomegaly from extramedullary hematopoiesis. Cranial nerve compression can lead to vision and hearing impairment. Growth delay and dental anomalies are common, and fractures are frequent due to increased bone brittleness. In milder autosomal dominant cases, hematologic symptoms may be less apparent, but bone pain and fractures can occur.

Diagnosis and imaging: Diagnosis relies on clinical presentation, family history, and imaging findings. Plain radiographs show diffuse osteosclerosis with reduced marrow spaces; skull bones are thickened, and the spine may display the “sandwich vertebra” or “bone within a bone” appearances.

Treatment and prognosis: There is no universal cure. Hematopoietic stem cell transplantation can be curative for the infantile malignant form by supplying functional osteoclast precursors. Supportive care includes management of anemia, infection prevention, dental surveillance, and treatment of cranial neuropathies. Prognosis varies by subtype, with severe forms carrying higher morbidity and mortality without transplantation, and milder forms allowing closer to normal life expectancy with complications.