title: Distal renal tubular acidosis associated with anion exchanger 1 mutations in children in Thailand.
abstract: BACKGROUND
  Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in hereditary distal renal tubular acidosis (dRTA). Hemoglobinopathies are common in Thailand. We analyzed AE1 and hemoglobin mutations in children in Thailand with dRTA to evaluate their association with clinical manifestations.
  
  
  METHODS
  Case series.
  
  
  METHODS
  17 patients were recruited from 6 referral hospitals in 4 regions of Thailand.
  
  
  METHODS
  AE1 mutations were detected by means of nucleotide sequence alterations. Hemoglobin E (HbE) was detected by means of hemoglobin typing, and thalassemia, by means of analysis of globin genes. Hemolytic anemia was indicated by decreased hemoglobin and hematocrit values in the presence of reticulocytosis.
  
  
  METHODS
  Leading clinical manifestations in patients were failure to thrive and muscle weakness. Compensated or overt anemia was identified in some cases. Coexistence of AE1 mutations with HbE or alpha(+)-thalassemia was present in a number of patients.
  
  
  RESULTS
  12 of 17 patients (70%) carried AE1 mutations, 7 patients (41%) had HbE, and 1 patient (6%) had alpha(+)-thalassemia. Patients with AE1 mutations presented with compensated hemolysis when they had metabolic acidosis. A patient with compound heterozygous Southeast Asian ovalocytosis/G701D and heterozygous alpha(+)-thalassemia showed severe hemolytic anemia.
  
  
  CONCLUSIONS
  5 patients (30%) without detectable AE1 mutation also were unknown for other genetic abnormalities.
  
  
  CONCLUSIONS
  Most of the patients with dRTA studied carried autosomal recessive AE1 mutations. Metabolic acidosis, which could be alleviated by adequate alkaline therapy, induced variable degrees of hemolysis in patients with dRTA associated with autosomal recessive AE1 mutations, especially in the presence of thalassemia.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Thammasat University, Bangkok, Thailand.
authors.forename: Sookkasem
authors.initials: S
authors.lastname: Khositseth
authors.forename: Apiwan
authors.initials: A
authors.lastname: Sirikanerat
authors.forename: Kulruedee
authors.initials: K
authors.lastname: Wongbenjarat
authors.forename: Sauwalak
authors.initials: S
authors.lastname: Opastirakul
authors.forename: Siri
authors.initials: S
authors.lastname: Khoprasert
authors.forename: Ratikorn
authors.initials: R
authors.lastname: Peuksungnern
authors.forename: Duangrurdee
authors.initials: D
authors.lastname: Wattanasirichaigoon
authors.forename: Wanna
authors.initials: W
authors.lastname: Thongnoppakhun
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
mesh_terms: D000141:Acidosis, Renal Tubular / Q000453:epidemiology / Q000235:genetics*; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D005293:Ferritins / Q000097:blood; D006453:Hemoglobinopathies / Q000453:epidemiology; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007223:Infant; D007686:Kidney Tubules, Distal; D008297:Male; D009154:Mutation; D009942:Organometallic Compounds; D013785:Thailand
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D006454:Hemoglobins; D009942:Organometallic Compounds; D005293:Ferritins; C062962:dirhodium tetraacetate