Genotype, Phenotype Correlations in Distal Renal Tubular Acidosis

Introduction
Distal renal tubular acidosis (dRTA) is characterized by an inability of α-intercalated cells in the distal nephron to secrete H+ ions into the urine. The individual may become chronically acidotic which results in growth retardation. The condition is also characterized by nephrocalcinosis, hypercalciuria, and hypocitraturia. The defect in acid secretion can either be acquired, usually seen in autoimmune conditions and drugs, or can be due to an inherited gene defect. Mutations causing dRTA have been found in several key transporters found in intercalated cells including the anion-exchanger 1 (AE1), H+ATPase, and cytosolic carbonic anhydrase II1–3. Classically it was though that mutations in AE1 were inherited in an autosomal dominant fashion and while H+ATPase in an autosomal recessive fashion2,3. Persons with H+ATPase mutations present earlier in life and the have a more severe phenotype than those with autosomal dominantly inherited AE1 mutations4.  Batlle has examined previous studies looking at individuals with dRTA and found that those with the AR form have lower serum potassium, lower serum pH, and lower bicarbonates than their AD counterparts5. However to our knowledge no one has compared the phenotypes of the two groups within the same center. Equally no one has previously examined the phenotype of those with SAO and compared it with the classic AE1 mutations.
Methods
Compared patients with documented mutations in AE1, H+ATPase. Phenotypic data collected including baseline electrolytes and pH. Urinary acidification test result, haematological results, and urine tests.
Results
We had a total of 26 patients with a documented mutation in one of the genes known to be responsible for causing dRTA. 5 were due to H+ATPase mutations, 19 were due to classic AE1 mutations (AD inheritance) and 2 had a mutation associated with SAO. 16 (62%) were female. Mean age in the 3 groups was 32, 46, and 33 in the H+ATPase, AD AE1, and SAO groups respectively. The baseline serum electrolytes and urine pH are displayed in table 1;