We have previously reported a large group of patients with endemic distal renal tubular acidosis (EdRTA) admitted to the hospitals in the northeast of Thailand. Since large number of patients were identified in a relatively short period of time, and in an area whose population is homogeneous, we were led to investigate the prevalence of the condition in the area. A survey was conducted in five villages (total population of 3,606) within the northeast of Thailand. 3,013 villagers were examined for urinary citrate concentration and short acid loading test was performed in those with low urinary citrate. 2.8% of the population (2.2-3.4%, 95% confidence interval) failed to lower their urine pH after acid loading; within this group, 0.8% of the population had serum potassium less than or equal to 3.5 mEq/l. In addition a large number of villagers were found to have low urinary citrate concentration and there was concurrent high prevalence of renal stone. The prevalence of EdRTA and renal stone was higher in villagers with poorer socioeconomic status, suggesting that environmental factors play a major role in their pathogenesis. Villagers with acidification defect have 2.4 times the chance of having renal stone and/or nephrocalcinosis. EdRTA is therefore one of the important factors responsible for the high prevalence of renal stone in the area. In conclusion we have confirmed the high prevalence of EdRTA in the northeast of Thailand and provided data showing high prevalence of renal stone and hypocitraturia in the same population.

Anion exchanger 1 (AE1 or SLC4A1) mutations have been reported to cause distal renal tubular acidosis (dRTA), a disease characterized by impaired acid excretion in the distal nephron. We have recently demonstrated homozygous AE1 G701D mutation as a common molecular defect of autosomal recessive (AR) dRTA in a group of Thai pediatric patients. In the present work, we discovered a de novo heterozygous AE1 R589C mutation, previously documented in inherited autosomal dominant (AD) dRTA. Arginine at this position is conserved in all vertebrate AE proteins indicating its functional importance. Three different mutations at this position (R589C, R589H, and R589S) were all found in AD dRTA and a de novo R589H mutation has previously been recorded. Our report is the second de novo mutation but with a different substituted amino acid. A high prevalence of AE1 R589 mutations and the presence of at least two de novo mutations at this position lead us to propose that codon 589 (CGC) is a "mutational hotspot" of AE1. The mechanism of recurrent mutations probably involves methylation and deamination altering cytosine (C) to thymine (T) in the CpG dinucleotides.A de novo R589C mutation of anion exchanger 1 causing distal renal tubular acidosis

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