Distal renal tubular acidosis is an uncommon renal disorder with a distal tubular acidification defect. It is characterized by inadequate net acid excretion resulting in a urine pH consistently above 6, hyperchloremic metabolic acidosis, growth impairment and in untreated cases, nephrocalcinosis and renal failure. It may occur as a primary condition, or as a secondary manifestation of a variety of underlying disorders, such as Sjogren's syndrome, use of amphotericin B and certain blood disorders such as sickle cell anaemia. Primary hereditary forms of distal renal tubular acidosis are predominantly seen as autosomal dominant traits. An autosomal recessive mode of inheritance has also been described in association or not with sensorineural deafness. In general, though not invariably, patients with dominant distal renal tubular acidosis display a milder phenotype than do those with recessively inherited disease. Some patients with autosomal dominant distal renal tubular acidosis remain asymptomatic until adolescence or adulthood, whereas others and those with recessive disease may be severely affected in infancy, with impaired growth and early NC eventually leading to renal insufficiency.

Mutations in the SLC4A1 gene, encoding the polytopic chloride-bicarbonate exchanger known as AE1, have been reported as the sole genetic cause of autosomal dominant distal renal tubular acidosis.

Mutations in the SLC4A1 gene, encoding the polytopic chloride-bicarbonate exchanger known as AE1, have been reported as the sole genetic cause of autosomal dominant distal renal tubular acidosis. Two main sites of AE1 expression are in erythrocyte cell membranes and, in the kidney, at the basolateral surface of a-intercalated cells in the collecting duct segment of the nephron. The encoded proteins are both products of SLC4A1, but because different promoters initiate transcription, they differ at their N termini, the renal isoform missing the first 65 amino acids found in the erythrocyte protein.