Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification

Pediatr Nephrol. 1997 Oct;11(5):633-6. doi: 10.1007/s004670050354.


Renal tubular acidosis with osteopetrosis is an autosomal recessive disorder due to deficiency of carbonic anhydrase II (CAII). A 3.5-year-old Egyptian boy with osteopetrosis and cerebral calcification has a persistent normal anion gap type of metabolic acidosis (plasma pH 7.26) and a mild degree of hypokalemia. A baseline urine pH was 7.0; ammonium (NH4+) excretion was low at 11 mumol/min per 1.73 m2; fractional excretion of bicarbonate HCO3 (FEHCO3) was high at 9% when plasma HCO3 was 20 mmol/l; citrate excretion rate was high for the degree of acidosis at 0.35 mmol/mmol creatinine. Intravenous administration of sodium bicarbonate led to a urine pH of 7.6, a FEHCO3 of 14%, a urine-blood PCO2 difference of 7 mmHg, NH4+ excretion fell to close to nil, and citrate excretion remained at 0.38 mmol/mmol creatinine. Intravenous administration of arginine hydrochloride caused the urine pH to fall to 5.8, the FEHCO3 to fall to 0, the NH4+ excretion rate to rise to 43 mumol/min per 1.73 m2, and citrate excretion to fall to < 0.01 mmol/mmol creatinine. These results show that our patient had a low rate of NH4+ excretion, a low urine minus blood PCO2 difference in alkaline urine, and a low urinary citrate excretion, but only when he was severely acidotic. He failed to achieve a maximally low urine pH. These findings indicate that his renal acidification mechanisms were impaired in both the proximal and distal tubule, the result of his CAII deficiency.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Renal Tubular / blood
  • Acidosis, Renal Tubular / enzymology*
  • Acidosis, Renal Tubular / pathology*
  • Ammonia / urine
  • Bicarbonates / metabolism
  • Carbonic Anhydrases / blood
  • Carbonic Anhydrases / deficiency*
  • Erythrocytes / enzymology
  • Humans
  • Infant
  • Male
  • Osteopetrosis / blood
  • Osteopetrosis / enzymology*
  • Osteopetrosis / pathology*


  • Bicarbonates
  • Ammonia
  • Carbonic Anhydrases