A novel TCIRG1 gene mutation leads to severe osteopetrosis with altered content of monocytes/macrophages in several organs.

Osteopetrosis (OP) is a clinically and genetically heterogeneous disease. Defects in the TCIRG1 gene are most frequently implicated in the osteoclast-rich form of OP. Little is known about the content and/or function of monocytes and macrophages of various organs rich in those cells in patients with OP. We report a patient with a novel TCIRG1 gene mutation that led to an osteoclast-rich OP. A bone marrow transplant failed to engraft, and the patient developed pulmonary hypertension. At autopsy he was found to have abnormal remodeling of the pulmonary vasculature and alveolar proteinosis. Alveolar macrophages were decreased. Pulmonary findings in this patient could be at least partially explained by abnormal surfactant metabolism due to depleted or defective alveolar macrophages.