Association between activating mutations of calcium-sensing receptor and Bartter's syndrome

Lancet. 2002 Aug 31;360(9334):692-4. doi: 10.1016/S0140-6736(02)09842-2.


Bartter's syndrome is a heterogeneous disorder characterised by deficient renal reabsorption of sodium and chloride, and hypokalaemic metabolic alkalosis with hyper-reninaemia and hyperaldosteronaemia. Mutations in several ion transporters and channels have been associated with the pathogenesis of Bartter's syndrome. We describe two hypocalcaemic patients with deficient parathyroid hormone secretion who also showed characteristics of Bartter's syndrome. We found activating mutations of the gene for the calcium-sensing receptor (CASR) in both patients. Activation of this calcium-sensing receptor inhibits the activity of a renal outer-medullary potassium channel that is mutated in type 2 Bartter's syndrome. We therefore suggest that some activating mutations of CASR could provide new mechanisms for the development of Bartter's syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bartter Syndrome / blood
  • Bartter Syndrome / complications
  • Bartter Syndrome / genetics*
  • Female
  • Humans
  • Hypocalcemia / complications
  • Hypoparathyroidism / complications
  • Male
  • Mutation
  • Parathyroid Hormone / deficiency
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics*


  • Parathyroid Hormone
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface