Carbonic Anhydrase II Deficiency in 12 Families with the Autosomal Recessive Syndrome of Osteopetrosis with Renal Tubular Acidosis and Cerebral Calcification

William S. Sly, Michael P. Whyte, Vasantha Sundaram, Richard E. Tashian, David Hewett-Emmett, Pierre Guibaud, Marc Vainsel, H. Jorge Baluarte, Alan Gruskin, M. al-Mosawi, Nadia Sakati, Arne Ohlsson

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223 Scopus citations

Abstract

Osteopetrosis with renal tubular acidosis and cerebral calcification was identified as a recessively inherited syndrome in 1972. In 1983, we reported a deficiency of carbonic anhydrase II, one of the isozymes of carbonic anhydrase, in three sisters with this disorder. We now describe our study of 18 similarly affected patients with this syndrome in 11 unrelated families of different geographic and ethnic origins. Virtual absence of the carbonic anhydrase II peak on high-performance liquid chromatography, of the esterase and carbon dioxide hydratase activities of carbonic anhydrase II, and of immunoprecipitable isozyme II was demonstrated on extracts of erythrocyte hemolysates from all patients studied. Reduced levels of isozyme II were found in obligate heterozygotes. These observations demonstrate the generality of the findings that we reported earlier in one family and provide further evidence that a deficiency of carbonic anhydrase II is the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. We also summarize the clinical findings in these families, propose mechanisms by which a deficiency of carbonic anhydrase II could produce this metabolic disorder of bone, kidney, and brain, and discuss the clinical evidence for genetic heterogeneity in patients from different kindreds with this inborn error of metabolism. (N Engl J Med 1985; 313:139–45.).

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalNew England Journal of Medicine
Volume313
Issue number3
DOIs
StatePublished - Jul 18 1985

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