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Carbonic anhydrase II (CA II) deficiency in man is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression symptoms, and dental malocclusion. The anemia and leukopenia seen in the recessive, lethal infantile form of osteopetrosis are not seen in CA II deficient patients. The renal tubular acidosis usually includes both proximal and distal components. Symptoms of metabolic acidosis respond to therapy, but no specific treatment is available for the osteopetrosis or cerebral calcification. We review here the role of carbonic anhydrases in bone resorption and renal acidification, and discuss clinical features and laboratory findings which distinguish CA II deficiency from other disorders producing osteopetrosis, renal tubular acidosis, or brain calcification. Methods to evaluate patients with pure proximal renal tubular acidosis for deficiency of CA IV are also discussed.

The content of carbonic anhydrase isozymes I (CA I) and II (CA II) in red blood cells and bone of osteopetrotic microphthalmic (mi/mi) mice was analyzed. Monospecific rabbit polyclonal antibodies against purified rat carbonic anhydrase I or II detected both isozymes in hemolysates of both normal and mi/mi mice. Total carbonic anhydrase activity measurements of hemolysates from normal or mi/mi mice were identical. A procedure based on bromopyruvate inactivation was devised to measure the relative contributions of CA I and II isozymes to the carbon dioxide hydration activity of hemolyzates. CA II dominates the observed activity of hemolysates of normal and mi/mi mice. Immunohistochemical studies showed that CA II was present in osteoclasts of tibial and calvarial bones of both normal and mi/mi mice. Thus, in contrast to the several cases of inherited osteopetrosis in humans, there is no lack of active CA II in erythrocytes of mi/mi mice. The absence of CA II, therefore, does not appear to play a role in the etiology of osteopetrosis in the mi/mi mouse.