Novel compound heterozygous ATP6V0A4 mutations in an infant with distal renal tubular acidosis.

A Japanese infant presenting with vomiting, failure to thrive, metabolic acidosis, and hyperammonemia was finally diagnosed with autosomal recessive distal renal tubular acidosis (dRTA). Hyperchloremic metabolic acidosis, hypokalemia, a normal serum anion gap, a positive urine anion gap, nephrocalcinosis, and high urine pH despite systemic acidemia were consistent with the cardinal manifestations in dRTA. Mutational analysis of the ATP6V0A4 gene revealed novel compound heterozygous mutations: Ile549fsX580 and Ile557Leu558del. The father was found to be heterozygote for the former mutation, the mother heterozygote for the latter. This is the first case of dRTA with hyperammonemia in which the ATP6V0A4 mutations were identified. dRTA should be considered in the differential diagnosis of children presenting with hyperammonemia. Additionally, in a possible case of autosomal recessive dRTA with normal hearing, mutational analysis of ATP6V0A4 gene may be recommended first to confirm the diagnosis.