Autosomal recessive malignant osteopetrosis (MIM 259700) is a rare congenital disorder of bone resorption affecting 1/200,000 individuals. The condition is caused by failure of osteoclasts to resorb immature bone. This results in abnormal bone marrow cavity formation and bone marrow failure. Clinical features of osteopetrosis include fractures (especially of the long bones), visual impairment, nerve compression resulting in headaches, blindness and deafness, haematological difficulties, unusual dentition, frequent infections, failure to thrive, and growth retardation. It is diagnosed immediately/shortly after birth and death can occur by 2 years due to severe anaemia, bleeding and /or infection. Osteopetrosis is generally diagnosed through skeletal X-rays. Bones appear unusually dense on X-rays with a chalky white appearance. Bone density tests and bone biopsies can also confirm a diagnosis.
Also known as
Autosomal recessive malignant osteopetrosis
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Clinically affected patients should if possible have their diagnosis confirmed by X-ray analysis, bone density tests and bone biopsies. The TCIRG1 gene located at 11q13, consists of 20 exons and encodes an a3 subunit of the vacuolar pump, which mediates acidification of bone/osteoclast interface. Mutations of this gene have been found in ~50% of autosomal recessive osteopetrosis patients. Mutation screening by direct sequencing is offered for exons 2 to 20 of the TCIRG1 gene in affected individuals.
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Great Ormond Street Hospital NE Thames Regional Genetics Service Laboratories
Great Ormond Street Hospital for Children
37 Queen Square
1ml EDTA neonates, 5ml EDTA adults
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Prenatals must be arranged in advance, through a Clinical Genetics department if possible. Amniotic fluid or CV samples should be sent to Cytogenetics for dissecting and culturing, with instructions to forward the sample to the Regional Molecular Genetics laboratory for analysis