title: Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome.
abstract: BACKGROUND
  Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria.
  
  
  OBJECTIVE
  The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment.
  
  
  METHODS
  Clinical, biological and genetic data were recorded in 26 patients.
  
  
  RESULTS
  Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (P=0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8 ± 0.3, 3.5 ± 0.5 and 3.2 ± 0.3 before treatment to 3.2 ± 0.5, 3.7 ± 0.6 and 3.7 ± 0.3 mmol/l with treatment in groups with two (P=0.003), one and no mutated alleles respectively.
  
  
  CONCLUSIONS
  In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.
authors.affiliation: Service d'Endocrinologie et Maladies Métaboliques, CHRU de Lille, 59037 Lille Cedex, France. asbalavoine@yahoo.fr
authors.forename: A S
authors.initials: AS
authors.lastname: Balavoine
authors.forename: P
authors.initials: P
authors.lastname: Bataille
authors.forename: P
authors.initials: P
authors.lastname: Vanhille
authors.forename: R
authors.initials: R
authors.lastname: Azar
authors.forename: C
authors.initials: C
authors.lastname: Noël
authors.forename: P
authors.initials: P
authors.lastname: Asseman
authors.forename: B
authors.initials: B
authors.lastname: Soudan
authors.forename: J L
authors.initials: JL
authors.lastname: Wémeau
authors.forename: M C
authors.initials: MC
authors.lastname: Vantyghem
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D048909:Diabetes Complications / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005838:Genotype; D053579:Gitelman Syndrome / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007008:Hypokalemia / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D011188:Potassium / Q000097:blood; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*; D055815:Young Adult
chemical_list: C412733:CLCNKB protein, human; D018118:Chloride Channels; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D000450:Aldosterone; D011188:Potassium