Distal RTA with nerve deafness: clinical spectrum and mutational analysis in five children

Distal renal tubular acidosis (RTA) with nerve deafness is caused by mutations in the ATP6V1B1 gene causing defective function of the H⁺-ATPase proton pump. We report five acidotic children (four males) from four unrelated families: blood pH 7.21–7.33, serum bicarbonate 10.8–14.7 mEq/l, minimum urinary pH 6.5–7.1 and fractional excretion of bicarbonate in the presence of normal bicarbonatemia 1.1–5.7%. Growth retardation and nephrocalcinosis, but not hypercalciuria, were common presenting manifestations. Hearing was normally preserved in one of the patients whose sister was severely deaf. One child was homozygous for a known mutation in exon 1: C>T (R31X). Three children were homozygous for a splicing mutation, intron 6 + 1G>A. The other patient was a compound heterozygote, having this mutation and a previously unreported mutation in exon 10: G>A (E330K). Our report shows that hearing loss is not always present in the syndrome of distal renal tubular acidosis with nerve deafness and the absence of hypercalciuria at diagnosis and describes a new mutation responsible for the disease in the ATP6V1B1 gene.