RENAL TUBULAR-ACIDOSIS AND OSTEOPETROSIS WITH CARBONIC-ANHYDRASE-II DEFICIENCY - PATHOGENESIS OF IMPAIRED ACIDIFICATION

Renal tubular acidosis with osteopetrosis is an autosomal recessive di sorder due to deficiency of carbonic anhydrase II (CAII). A 3.5-year-o ld Egyptian boy with osteopetrosis and cerebral calcification had a pe rsistent normal anion gap type of metabolic acidosis (plasma pH 7.26) and a mild degree of hypokalemia. A baseline urine pH was 7.0; ammoniu m (NH4+) excretion was low at 11 mu mol/min per 1.73 m(2); fractional excretion of bicarbonate HCO3 (FEHCO3) was high at 9%, when plasma HCO 3 was 20 mmol/l; citrate excretion rate was high for the degree of aci dosis at 0.35 mmol/mmol creatinine. Intravenous administration of sodi um bicarbonate led to a urine pH of 7.6, a FEHCO3 of 14%, a urine-bloo d PCO2 difference of 7 mmHg, NH4+ excretion fell to close to nil, and citrate excretion remained at 0.38 mmol/mmol creatinine. Intravenous a dministration 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 m u mol/min per 1.73 m(2), and citrate excretion to fall to <0.01 mmol/m mol creatinine. These results show that our patient had a low rate of NH4+ excretion, a low urine minus blood PCO2 difference in alkaline ur ine, and a low urinary citrate excretion, but only when he was severel y acidotic. He failed to achieve a maximally low urine pH, These findi ngs indicate that his renal acidification mechanisms were impaired in both the proximal and distal tubule, the result of his CA(II) deficien cy.