title: Autosomal recessive distal renal tubular acidosis associated with Southeast Asian ovalocytosis.
abstract: BACKGROUND
  A defect in the anion exchanger 1 (AE1) of the basolateral membrane of type A intercalated cells in the renal collecting duct may result in a failure to maintain a cell-to-lumen H+ gradient, leading to distal renal tubular acidosis (dRTA). Thus, dRTA may occur in Southeast Asian ovalocytosis (SAO), a common AE1 gene abnormality observed in Southeast Asia and Melanesia. Our study investigated whether or not this renal acidification defect exists in individuals with SAO.
  
  
  METHODS
  Short and three-day NH4Cl loading tests were performed in 20 individuals with SAO and in two subjects, including their families, with both SAO and dRTA. Mutations of AE1 gene in individuals with SAO and members of the two families were also studied.
  
  
  RESULTS
  Renal acidification in the 20 individuals with SAO and in the parents of the two families was normal. However, the two clinically affected individuals with SAO and dRTA had compound heterozygosity of 27 bp deletion in exon 11 and missense mutation G701D resulting from a CGG-->CAG substitution in exon 17 of the AE1 gene. Red cells of the two subjects with dRTA and SAO and the family members with SAO showed an approximate 40% reduction in sulfate influx with normal 4,4'-di-isothiocyanato-stilbene-2,2'-disulfonic acid sensitivity and pH dependence.
  
  
  CONCLUSIONS
  These findings suggest that compound heterozygosity of abnormal AE1 genes causes autosomal recessive dRTA in SAO.
authors.affiliation: Renal Division, Siriraj Hospital, Mahidol University, Bangkok, Thailand. sisva@mucc.mahidol.ac.th
authors.forename: S
authors.initials: S
authors.lastname: Vasuvattakul
authors.forename: P T
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: P
authors.initials: P
authors.lastname: Vachuanichsanong
authors.forename: P
authors.initials: P
authors.lastname: Thuwajit
authors.forename: C
authors.initials: C
authors.lastname: Kaitwatcharachai
authors.forename: V
authors.initials: V
authors.lastname: Laosombat
authors.forename: P
authors.initials: P
authors.lastname: Malasit
authors.forename: P
authors.initials: P
authors.lastname: Wilairat
authors.forename: S
authors.initials: S
authors.lastname: Nimmannit
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D001483:Base Sequence; D027963:Chloride-Bicarbonate Antiporters; D004612:Elliptocytosis, Hereditary / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism; D005808:Genes, Recessive; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters