Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D).
Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world.
Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in <i>ATP6V0A4-</i>, <i>ATP6V1B1-</i>, and <i>FOXI1-</i>dRTA), and hereditary hemolytic anemia (in some individuals with <i>SLC4A1-</i>dRTA).
Our study shows that the compound E522K/G701D mutation of human anion exchanger 1 causes a trafficking defect in kidney cells, and this may explain the complete distal renal tubular acidosis of the patient.
Mutations in SLC4A1, encoding the chloride-bicarbonate exchanger AE1, cause distal renal tubular acidosis (dRTA), a disease of defective urinary acidification by the distal nephron.
Several studies have shown trafficking defects in the mutant protein rather than the lack of function as the major mechanism underlying the pathogenesis of dRTA from AE1 mutations.
However, recent studies of Thai dRTA families have shown that mutations in this gene result in autosomal recessive (AR) dRTA, giving rise to the postulation that AE1 gene mutations causing AR dRTA might be found commonly in Thai pediatric patients with dRTA.
We searched for SLC4A1 gene mutations in six patients from a Chinese family with a severe phenotype of dRTA (growth impairment, severe metabolic acidosis, with/or without gross nephrocalcinosis and renal impairment).
This study is considered as a pilot study showing the importance of AE1 mutations in Iranian children with DRTA and further studies is recommended in this geographic region of the world.
Mutations in SLC4A1 that mislocalize its product, the chloride/bicarbonate exchanger AE1, away from its normal position on the basolateral membrane of the α-intercalated cell cause autosomal dominant distal renal tubular acidosis (dRTA).