Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes.
Inherited hypokalemic metabolic alkalosis, or Bartter syndrome, comprises several closely related disorders of renal tubular electrolyte transport. Recent advances in the field of molecular genetics have demonstrated that there are four genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Neonatal Bartter syndrome affects neonates and is characterized by polyhydramnios, premature delivery, severe electrolyte derangements, growth retardation, and hypercalciuria leading to nephrocalcinosis. It may be caused by a mutation in the gene encoding the Na-K-2Cl cotransporter (NKCC2) or the outwardly rectifying potassium channel (ROMK), a regulator of NKCC2. Classic Bartter syndrome is due to a mutation in the gene encoding the chloride channel (CLCNKB), also a regulator of NKCC2, and typically presents in infancy or early childhood with failure to thrive. Nephrocalcinosis is typically absent despite hypercalciuria. The hypocalciuric, hypomagnesemic variant of Bartter syndrome (Gitelman syndrome), presents in early adulthood with predominantly musculoskeletal symptoms and is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT). Even though our understanding of these disorders has been greatly advanced by these discoveries, the pathophysiology remains to be completely defined. Genotype-phenotype correlations among the four disorders are quite variable and continue to be studied. A comprehensive review of Bartter and Gitelman syndromes will be provided here.
Shaer
A J
AJ
Division of Nephrology, Medical University of South Carolina, Charleston 29425, USA. shaeraj@musc.edu
D000471:Alkalosis / Q000145:classification / Q000209:etiology / Q000235:genetics*; D001477:Bartter Syndrome / Q000145:classification / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins; D006801:Humans; D007008:Hypokalemia / Q000145:classification / Q000209:etiology / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D015499:Renal Tubular Transport, Inborn Errors / Q000145:classification / Q000209:etiology / Q000235:genetics*; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D013577:Syndrome
D002352:Carrier Proteins; C086989:KCNJ1 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C578714:SLC12A1 protein, human; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor