Síndromes de Bartter y Gitelman: revisión de los aspectos genéticos, fisiopatológicos y clínicos

Bartter and Gitelman syndromes are hereditary disorders characterized by a remarkable reduction of salt transportation by the thick ascending limb of the Henle's loop. Consequently, patients suffering from Bartter syndrome present with renal salt wasting, low blood pressure, hypokalemic metabolic alkalosis and hypercalciuria, and are at risk of developing renal stones. Based on recent studies, the Bartter syndrome has been subdivided into five types according to the genetic defect involved and the phenotype: type 1 is caused by a mutation in the gene coding for the chloride, sodium, and potassium co–transporter; type 2 is due to a mutation in the gene coding for the ROMK potassium channel. These two genetic variations are jointly denominated neonatal Bartter syndrome, because of their early clinical presentation, with maternal polyhydramnios, prematurity, severe polyuria and high levels of E2 prostaglandine. Type 3, also known as classic Bartter syndrome, is produced by mutations in the gen that codes for the chloride CLC–Kb channel; this type is detected since childhood with growth delay, polyuria, polydipsia and anorexia. Type 4, which is associated with neurosensorial deafness, is characterized by a mutation in the gen that codes for the Barttin protein which is a part of the CLC–Kb and CLC–Ka chloride channels. Type 5 appears because of a mutation in the gene that codes for a calcium receptor located at the basolateral membrane of the ascending limb of Henle's loop; patients with this type develop parathormone deficit, as well as the symptoms that are common to all types of the syndrome. The phenotype of Gitelman syndrome is less severe and its clinical presentation is delayed; it differs from the Bartter syndrome in that patients have hypomagnesemia and hipocalciuria. They may be asymptomatic or show transitory muscular weakness, paresthesias, paralysis and even cardiac rhythm alterations. Recent advances in molecular genetics have made it possible to distinguish between the different clinical types and are the basis for several therapeutic options. This review includes genetic, physiopathological and clinical aspects of the Bartter and Gitelman syndromes.