Carbonic anhydrase II deficiency: diagnosis and carrier detection using differential enzyme inhibition and inactivation

Am J Hum Genet. 1986 Feb;38(2):125-36.


Carbonic anhydrase (CA) I and II are soluble isozymes that represent the major nonhemoglobin proteins in the erythrocyte. We recently identified a deficiency of CA II as the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Virtual absence of the CA II peak on high-performance liquid chromatography, of CA II esterase activity, and of immunoprecipitable CA II were demonstrated on extracts of red cell lysates from all patients studied. Reduced levels of CA II were found in obligate heterozygotes. Here, we present evidence that CA II in red cell lysates can be quantitated by measuring CO2 hydratase activity in the presence of inhibitors that selectively inhibit the activity of CA I to a much greater extent than that of CA II. This was done with iodide (anion binding) and bromopyruvic acid (alkylation), and the respective assays evaluated as diagnostic tools for CA II deficiency in human red cells. These techniques greatly simplify the quantitation of CA II in hemolysates and should make genetic diagnosis and counseling for the newly described inborn error of metabolism due to CA II deficiency generally available. They also allow quantitation of CA I in red cell lysates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis, Renal Tubular / complications
  • Acidosis, Renal Tubular / diagnosis
  • Acidosis, Renal Tubular / genetics
  • Brain Diseases / complications
  • Brain Diseases / diagnosis
  • Brain Diseases / genetics
  • Calcinosis / complications
  • Calcinosis / diagnosis
  • Calcinosis / genetics
  • Carbonic Anhydrase Inhibitors*
  • Carbonic Anhydrases / blood
  • Carbonic Anhydrases / deficiency*
  • Carbonic Anhydrases / genetics
  • Clinical Enzyme Tests*
  • Erythrocytes / enzymology
  • Female
  • Genetic Carrier Screening*
  • Humans
  • Isoenzymes / blood
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics
  • Male
  • Osteopetrosis / complications
  • Osteopetrosis / diagnosis
  • Osteopetrosis / genetics
  • Pedigree
  • Pyruvates / pharmacology
  • Sodium Iodide / pharmacology
  • Syndrome


  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Pyruvates
  • bromopyruvate
  • Carbonic Anhydrases
  • Sodium Iodide