Distal renal tubular acidosis associated with anion exchanger 1 mutations in children in Thailand.
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.
Khositseth
Sookkasem
S
Department of Pediatrics, Faculty of Medicine, Thammasat University, Bangkok, Thailand.
Sirikanerat
Apiwan
A
Wongbenjarat
Kulruedee
K
Opastirakul
Sauwalak
S
Khoprasert
Siri
S
Peuksungnern
Ratikorn
R
Wattanasirichaigoon
Duangrurdee
D
Thongnoppakhun
Wanna
W
Viprakasit
Vip
V
Yenchitsomanus
Pa-Thai
PT
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
D001457:Anion Exchange Protein 1, Erythrocyte; D006454:Hemoglobins; D009942:Organometallic Compounds; D005293:Ferritins; C062962:dirhodium tetraacetate