This is the classical RTA disease, Type 1, not Types 2-4 which are heterogenous, rarer and less well understood. Basic defect in dRTA is renal inability of excrete urine more acid than pH 5.3 (H+ 5 μmol/l), a fault in the alpha-intercalated cell of renal cortical collecting duct, where 3 metabolic processes are involved – 1) hydration of dissolved carbon dioxide to proton and bicarbonate, catalyzed by CA II, 2) proton secretion through apical membrane, 3) bicarbonate reclamation by anion-exchanger in basolateral membrane. dRTA can result from damage to any of these. Commonest cause of dRTA is autoimmune in post-pubertal women, causing loss of 2), 3) or both, or global destruction of whole alpha-intercalated cell. Defects in apical proton secretion from gene mutations cause occidental recessive dRTA. Defects in baso-lateral chloride/bicarbonate exchanger, through SLC4A1 mutations, cause rare but universally distributed dominant dRTA. Southeast Asian dRTA is recessive and has high local incidence, almost invariably the result of homozygous or compound heterozygous SLC4A1 mutations that have never been recorded in the west, and cause profound red-cell morphological changes and increased haemolysis. These mutations may have evolved as protection against Plasmodium falciparum malaria.