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

Abstract.

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 had 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 μmol/min per 1.73 m²; fractional excretion of bicarbonate HCO₃ (FE_HCO3) 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 FE_HCO3 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 FE_HCO3 to fall to 0, the NH₄ ⁺ excretion rate to rise to 43 μmol/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 CA_II deficiency.