Atypical distal renal tubular acidosis confirmed by mutation analysis

In autosomal dominant distal renal tubular acidosis type I (dRTA) impaired hydrogen ion secretion is associated with metabolic acidosis, hyperchloremi c hypokalemia, hypercalciuria, nephrocalcinosis, and/or nephrolithiasis. A retardation of growth is commonly observed. In this report we present a fam ily with autosomal dominant dRTA with an atypical and discordant clinical p icture. The father presented with severe nephrocalcinosis, nephrolithiasis, and isosthenuria but metabolic acidosis was absent. His 6-year-old daughte r, however, suffered from metabolic acidosis, hypokalemia, and hypercalciur ia. In addition, sonography revealed multiple bilateral renal cysts but no nephrocalcinosis. Mutation analysis of the AE1 gene coding for the renal Cl -/HCO3--exchanger AE1 displayed a heterozygous Arg589Cys exchange in both p atients but not in the healthy family members. This point mutation is frequ ently associated with autosomal dominant dRTA. Diagnosis of autosomal domin ant dRTA is supported in this family by results of AE1 mutation analysis.