LAUSR

A 5-month-old baby girl presented to our hospital with frontal bossing, splenomegaly, leukocytosis, anemia, and thrombocytopenia. Her neonatal course was complicated by a seizure episode. Workup at that time revealed severe hypocalcemia, low vitamin D levels, and significantly elevated parathyroid hormone. She was treated with calcium and vitamin D supplementation with no further seizure episodes. Upon presentation, a chest x-ray was performed, showing expanded costochondral junctions, sclerotic, dense ribs, and an expanded and splayed metaphyses of the bilateral humeri. Radiograph of the pelvis and lower limbs showed a “bone within bone” appearance with fraying and splaying of the metaphysis. A bone marrow biopsy showed marked thickening of the bony trabeculae and marked reduction in medullary cavity and hematopoietic precursors, with increased connective tissue. The bones were irregular and contained cartilaginous plates. There were numerous osteoclasts along the endosteal surface (Figs. 1–5). Laboratory and radiologic findings in this baby were pathognomonic for a diagnosis of infantile malignant osteopetrosis. Further workup included a computed tomographic scan of the orbits which showed narrowed optic canals bilaterally and ophthalmologic evaluation revealed optic nerve atrophy. The infant’s 3-year-old sister was found to be an HLA-identical match and she was referred for hematopoietic stem cell transplantation. Whole exome sequencing was sent on the infant and both parents to identify the causative genetic mutation, which revealed a compound heterozygous TCIR1G1 mutation. The baby is now 4 months after transplant and doing well. Osteopetrosis is a rare genetic disorder of osteoclast production and function, characterized by impaired bone resorption and increased bone sclerosis.1 Affected children invariably develop blindness, deafness, and death by age 10 from bone marrow failure. The mainstay of diagnosis is clinical and largely depends on the radiographic appearance of the skeleton. The classic radiologic features of osteopetrosis comprise: diffuse sclerosis, affecting the skull, spine, pelvis and appendicular bones, bone modeling defects at the metaphyses of long bones, “bone-in-bone” appearance particularly in the vertebrae and phalanges, and focal sclerosis of the skull base, pelvis, and vertebral end plates.2,3 Age of onset, inheritance pattern, and the presence of associated features, may point to particular subtypes of osteopetrosis. Genetic testing can be used to confirm the diagnosis and differentiate between subtypes.3 FIGURE 1. Bone marrow core biopsy, hematoxylin and eosin, showing marked thickening of the irregular bony trabeculae and reduction in medullary cavity.