Osteopetrosis, Autosomal recessive 3 (OPTB3)

(OMIM phenotype number #259730)

Osteopetrosis, Autosomal recessive 3, is a rare form of autosomal recessive osteopetrosis (see OPTB1) caused by homozygous or compound heterozygous mutation in the gene encoding carbonic anhydrase II (CA2 gene). This disorder is characterized by a triad of osteopetrosis, renal tubular acidosis, and neurological disorders related to cerebral calcifications. Other clinical manifestations are: an high risk of fractures, dental abnormalities, cranial nerve compression, developmental delay and short stature. The radiographic exams can show cerebral calcifications by early childhood. The osteosclerosis and skeletal modeling defects may gradually resolve by adulthood. Renal tubular acidosis (proximal, distal, or combined type) can cause hyperchloremic metabolic acidosis, sometimes with hypokalemia. Nearly 100 cases have been described, predominantly from the Middle East and Mediterranean region, but cases have been documented worldwide.

Currently, there is no established medical therapy.


CA2 gene, 8q21.2 (OMIM gene/locus number #611492), enconding carbonic anhydrase, expressed at high levels in OCs during bone resorption. Several different mutations within the CA2 gene have been identified.


Intermediate form, renal tubular acidosis (typical sign), basal ganglion calcification (typical sign), early fractures, short stature, dental malocclusion, increased bone density (sclerosis) and generalized high bone mass, diaphyseal sclerosis, cranial hyperostosis, normal intelligence or mental retardation, visual impairment, hepatosplenomegaly, anemia (not usual), extramedullary hematopoiesis.

Main biochemical alterations

Adult/intermediate forms: high CK-BB, high bone ALP. Infantile/severe forms: low Ca, high PTH, high 1,25(OH)2D, high CK-BB, high AP, anemia, metabolic acidosis.

Other resource

Osteopetrosis Society (OPETS)


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  5. http://www.omim.org