P77 – 2515: Case of generalized osteopetrosis (marble disease) associated with neurological impairment

Abstract

Objective Marble bone disease is an inherited condition, characterized by diffuse hardening of bones, their brittleness due to malfunction of osteoclasts. Secondary to bone expansion bone marrow narrows, extramedullar hemopoesis develops, nerves injury might happen. Mutations in 9 genes had been described. CLCN7 mutation leads to 75% cases of autosomal dominant osteopetrosis with benign course, 10 to 15% cases are autosomal recessive with malignant course. Methods A child was born uneventfully from healthy, non-consanguineous parents. First signs of illness appeared at 10 weeks when parents noted tense fontanelle, child became very irritated, horizontal nystagmus appeared, development had stopped. At 6 months the child neither fixed nor followed, but reacted positively to the mother's voice, smiled, had horizontal nystagmus, tetraparesis, diffuse hypotonia, high tendon reflexes, head circumference – 40 cm. Brain MRI showed signs of Chiari I malformation, hypogenesis of corpus callosum, ventriculodilation of lateral ventriculi (12 mm on the level of frontal horn) dilation of fronto – temporal subarhnoid spaces of 7–8 mm, decreased volume of white matter, cerebellum tonsillar herniation of 6 mm. Laboratory finding showed: LDH – 1093, AST – 103, Hgb – 81 g/l, Plt – 72×10 9 /l, WBC under 3×10 9 /l, Chitotriosidase 80 (78–120) nmol/g/mg/protein. USD demonstrated tenfold increasing of spleen size. EMG showed secondary myopathic syndrome. X-ray revealed typical sign of osteopetrosis – “bone in bone” syndrome, clavate thickening of metaphyses, ostesclerosis of pelvis and femurs. Horizontal nystagmus, partial atrophy of optic nerves. Results We made the diagnosis of generalized osteopetrosis, autosomal recessive form, hematology syndrome (anemia, thrombocytopenia, hepatosplenomegaly), bones deformities, development retardation. Genetic risk for sibs is 25%. The disease had malignant course. Despite symptomatic treatment the child had died aged 17 months. Conclusion Presented case of generalized osteopetrosis illustrates progressive course of the disease, with hematologic syndrome and involvement of neurological system, that lead to first presentation of the patient to neurology clinic