Chloride channel CICN7 mutations in a Korean patient with infantile malignant osteopetrosis initially presenting with neonatal thrombocytopenia.

Infantile malignant Osteopetrosis (Autosomal Recessive Osteopterosis, ARO, MIM 259700) is a genetically heterogenous autosomal recessive disorder of bone metabolism, which, if untreated, has a fatal outcome. Early death is common, with only 30% survival at 6 years of age. It is characterized by generalized osteosclerosis, secondary to bone marrow failure with anemia and thrombocytopenia with subsequent extramedullary hematopoiesis and impaired vision and hearing due to encroachment of nerve canals. Other presentations include failure to thrive and recurrent infections, both secondary to the underlying anemia and bone marrow involvement. A defect in macrophage killing of bacteria may account for recurrent and sometimes overwhelming infection. Hypocalcemic seizures, excessive bruising, nontraumatic fractures, abnormal craniofacial appearance (macrocephaly and frontal bossing) and snuffling because of disruption of nasal architecture are also less common complaints. Neurological involvement can range from mild developmental delay to generalized neurodegeneration, which may be associated with primary retinal degeneration. In this investigation, we describe a patient with apparent clinical features of ARO bearing two mutations in ClCN7 gene, who died of overwhelming sepsis at 5 months of age despite medical management with high-dose vitamin D, IFN-, and steroid.