Malignant infantile osteopetrosis initially presenting with neonatal hypocalcemia: case report

Abstract.

Autosomal recessive "malignant" osteopetrosis is a rare congenital disorder relating to bone resorption abnormalities. It is believed to arise due to the failure of osteoclasts to resorb immature bone. This leads to abnormal bone marrow cavity formation and, clinically, to the signs and symptoms of bone marrow failure. Impaired bone remodeling associated with dysregulated activity of osteoclasts for such a condition may typically result in bony narrowing of the cranial nerve foramina, which typically results in cranial nerve (especially optic nerve) compression. Abnormal remodeling of primary woven bone to lamellar bone results in "brittle" bone that is prone to fracture. Thus, fractures, visual impairment, and bone marrow failure are the classical features of this disease. We describe the case of a 23-day-old boy in whom neonatal hypocalcemia was present initially after birth. Malignant infantile osteopetrosis (MIO) was diagnosed for the patient at 4 months of age based on evidence of anemia, thrombocytopenia, leukoerythroblastosis, sclerotic bone, hepatosplenomegaly, and visual deficit from a bony encroachment by the cranial nerve foramina. Although only occasionally reported previously, MIO remains essentially unrecognized by clinicians as a cause of neonatal hypocalcemia, which often results in diagnostic confusion and delay. This is important in the context of curative hemopoietic stem cell transplantation where preservation of sight may depend upon early intervention.