The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes

Molecular defects affecting the transport of sodium, potassium and chloride in the nephron through the ROMK K+ channel, Na+/K+/2Cl(-) cotransporter, t he Na+/CT cotransporter and chloride channel have been identified in patien ts with Bartter's and Gitelman's syndromes. Defects of the angiotensin II t ype I receptor and CFTR have also being described. These defects are simple (ie, most are single amino acid substitutions) but affect key elements in tubular transport. The simplicity of the genetic defects may explain why th e inheritance of these conditions remains unclear in most kindreds (ie, not just recessive or dominant) and emphasises the crucial importance of the c onformational structure of these channels. Application of this molecular in formation will allow the early genetic identification of patients with thes e syndromes and enable us to differentiate between the various disorders at a functional level. It may also identify a subgroup in which the heterozyg ous form may make patients potentially exquisitely sensitive to diuretics.