[Juvenile malignant osteopetrosis. Clinico-radiological study of 7 cases]

Clinical and radiological studies of seven patients with autosomic recessive malignant osteopetrosis are presented. Diagnosis was established before the age of 3 months in six cases and at 7 months in one. In all cases the presenting signs were pallor and hepatosplenomegaly with associated neurological involvement in five. All patients had normocytic normochromic anemia, leucopenia and thrombocytopenia with features of extramedullary hematopoiesis. Radiological studies revealed increase in the density of bones with "mask" appearance of facial bones and diminished size of optic foramina. Long bones showed absence of normal trabeculae and anomalies in modeling with methaphiseal bands and "bone within bone" images. There was hypocalcemia and hypophosphatemia with slight increases in alkaline phosphatase; parathormone was normal. Clinical course was characterized by progressive pancytopenia, recurrent infections and neurological deterioration with convulsions, nistagmus and optic atrophy. Five out of the seven patients died after a median of 3 months, due to infections or haemorrhage. The patient diagnosed at 7 months of age presented bilateral optic atrophy and moderate anemia; no other complications appeared after 2 year follow-up. Histological findings included substitution of bone marrow by chondro-osseous tissue; focal obsteoblastic and osteoclastic activity in calcified cartilage, and myeloid metaplasia in liver, spleen, lymph nodes and kidneys. The lesions are in agreement with the concept of a defect in bone formation-resorbtion balance; dysfunction of both osteoclasts and osteocytes is implicated in the pathogenesis. Unlike experimental disease, osteopetrosis in man is probably an heterogeneous disease and appropriate therapy should be individualized. Nevertheless, at present, the only favorable results have been obtained with bone-marrow transplantation.