Inherited renal tubular acidosis

The past few years have witnessed great progress in elucidating the molecular basis of inherited renal tubular acidosis. Consistent with the physiologically defined importance of multiple gene products in urinary acidification, heritable renal tubular acidosis is genetically heterogeneous. Autosomal dominant distal renal tubular acidosis has been associated with a small number of mutations in the AE1 Cl-/HCO3- exchanger although the pathophysiologic mechanisms behind these mutations remain unclear. Rarely, autosomal recessive distal RTA is caused by homozygosity or compound heterozygosity for the loss-of-function mutation AE1 G701D. A larger proportion, often accompanied by hearing loss, is associated with mutations in the ATP6B1 gene encoding the 58 kDa B1 subunit of the vacuolar H+-ATPase. Mutations in the gene encoding the Na+/HCO3- cotransporter, NBC1, have recently been identified in proximal renal tubular acidosis with corneal calcification.