title: Life-threatening metabolic alkalosis in Pendred syndrome.
abstract: BACKGROUND
  Pendred syndrome, a combination of sensorineural deafness, impaired organification of iodide in the thyroid and goitre, results from biallelic defects in pendrin (encoded by SLC26A4), which transports chloride and iodide in the inner ear and thyroid respectively. Recently, pendrin has also been identified in the kidneys, where it is found in the apical plasma membrane of non-α-type intercalated cells of the cortical collecting duct. Here, it functions as a chloride-bicarbonate exchanger, capable of secreting bicarbonate into the urine. Despite this function, patients with Pendred syndrome have not been reported to develop any significant acid-base disturbances, except a single previous reported case of metabolic alkalosis in the context of Pendred syndrome in a child started on a diuretic.
  
  
  METHODS
  We describe a 46-year-old female with sensorineural deafness and hypothyroidism, who presented with severe hypokalaemic metabolic alkalosis during inter-current illnesses on two occasions, and who was found to be homozygous for a loss-of-function mutation (V138F) in SLC26A4. Her acid-base status and electrolytes were unremarkable when she was well.
  
  
  CONCLUSIONS
  This case illustrates that, although pendrin is not usually required to maintain acid-base homeostasis under ambient condition, loss of renal bicarbonate excretion by pendrin during a metabolic alkalotic challenge may contribute to life-threatening acid-base disturbances in patients with Pendred syndrome.
authors.affiliation: Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Kandasamy
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Mark
authors.initials: M
authors.lastname: Evans
authors.forename: Krishna
authors.initials: K
authors.lastname: Chatterjee
authors.forename: Fiona
authors.initials: F
authors.lastname: Karet
mesh_terms: D000437:Alcoholism / Q000150:complications; D000471:Alkalosis / Q000209:etiology* / Q000235:genetics; D005260:Female; D006044:Goiter, Nodular / Q000150:complications / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D020125:Mutation, Missense; D000076988:Sulfate Transporters
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters