Bartter syndrome: unraveling the pathophysiologic enigma.
Familial hypokalemic, hypochloremic metabolic alkalosis, or Bartter syndrome, is not a single disorder but rather a set of closely related disorders. These Bartter-like syndromes share many of the same physiologic derangements, but differ with regard to the age of onset, the presenting symptoms, the magnitude of urinary potassium (K) and prostaglandin excretion, and the extent of urinary calcium excretion. At least three clinical phenotypes have been distinguished: (1) classic Bartter syndrome; (2) the hypocalciuric-hypomagnesemic Gitelman variant; and (3) the antenatal hypercalciuric variant (also termed hyperprostaglandin E syndrome). The fundamental pathogenesis of this complex set of disorders has long fascinated and stymied investigators. Physiologic investigations have suggested numerous pathogenic models. The cloning of genes encoding renal transport proteins has provided molecular tools to begin testing these hypotheses. To date, molecular genetic analyses have determined that mutations in the gene encoding the thiazide-sensitive sodium-chloride (Na-Cl) cotransporter underlie the pathogenesis of the Gitelman variant. In comparison, the antenatal variant is genetically heterogeneous with mutations in the genes encoding either the bumetanide-sensitive sodium-potassium-chloride (Na-K-2Cl) cotransporter or the luminal, ATP-regulated, K channel. With these data, investigators have begun to unravel the pathophysiologic enigma of the Bartter-like syndromes. Further studies will help refine pathogenic models for this set of disorders as well as provide new insights into the normal mechanisms of renal electrolyte transport.
Guay-Woodford
L M
LM
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
D001477:Bartter Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D003937:Diagnosis, Differential; D006801:Humans; D007686:Kidney Tubules, Distal / Q000503:physiopathology; D011379:Prognosis; D013577:Syndrome