Increased Bone Density in a Newborn

Abstract

Increased bone density in a newborn.The male infant is referred at 22 days of age to a children’s hospital due to severe pallor.Evaluation of the infant’s mother revealed a complete blood count within normal limits and negative results on antinuclear antibody test, leukocyte esterase cell preparation, and anticardiolipin antibody assessement.Abdominopelvic ultrasonography: Mild hepatosplenomegalyThe findings on chest radiography suggested the diagnosis of MIO, which was confirmed with a bone survey. Hematologic consultation was obtained; treatment was initiated with high doses of vitamin D, gamma-interferon, and prednisolone; and the parents were referred for genetic counseling.The infant was discharged after 2 weeks while receiving the previously noted therapy, and arrangements were made for follow-up evaluation and possible bone marrow transplantation.Osteopetrosis is an extremely rare hereditary bone disorder in which defective bone resorption by osteoclasts leads to excessive bone deposition. Different forms have been described, with radiologic and clinical features varying from mild to severe. The conditions can be inherited as autosomal recessive, autosomal dominant, or X-linked traits, with the most severe forms being autosomal recessive.MIO is an autosomal recessive disorder that presents within the first few months after birth. The filling of marrow cavities by hyperostotic bones results in bone marrow failure, with profound anemia and thrombocytopenia associated with extramedullary hematopoiesis and hepatosplenomegaly. Longitudinal bone growth is impaired, resulting in varying degrees of short stature.Radiography is the gold standard for diagnosis and largely depends on the radiographic appearance of the skeleton. The radiographic hallmarks of osteopetrosis include:This patient’s bones were diffusely dense, chalky, and white. Such an appearance explains why the condition also has been named “marble bone disease.”The distal ends of the bones also were frayed, an early sign of rickets. Rickets in osteopetrosis is due to calcium deficiency. Although body calcium stores are high, calcium cannot be released from the bones because of the defective function of osteoclasts. Long bones show densely sclerotic bones, with poor differentiation between the cortex and medullary cavity, characteristic of osteopetrosis.The primary goals of therapy in patients who have severe malignant osteopetrosis are to prolong survival, delay disease progression, and manage secondary complications. Presently, bone marrow transplantation is the only potentially curative therapy, but successful transplantation depends on the availability of a suitably matched donor, which can be found for only 20% to 40% of patients. For the remaining patients, therapy is aimed at slowing the progression of disease and managing secondary complications such as anemia and recurrent infections. Infantile osteopetrosis warrants treatment because of the adverse outcome associated with the disease.Several therapeutic agents have been suggested as supportive therapy:The prognosis for MIO is uniformly poor in the absence of bone marrow transplantation. Most affected children succumb to the disease by mid-childhood due to anemia, bleeding, and infections. Early diagnosis is very important to allow early intervention. Delay in diagnosis and early intervention for MIO frequently is due to the condition essentially remaining unrecognized by clinicians as a cause of neonatal anemia and thrombocytopenia. The diagnosis of osteopetrosis should be considered for any neonate who has anemia and thrombocytopenia whose parents are consanguineous, especially if the infant has hepatosplenomegaly, and appropriate radiologic studies should be obtained.JoDee M. Anderson, MD, MEd, Division of Neonatal Medicine, Oregon Health & Science University, Portland, OR