Early-onset autosomal dominant distal renal tubular acidosis caused by a de novo SLC4A1 R589C variant with growth failure and rickets.

Autosomal dominant (AD) distal renal tubular acidosis (dRTA) generally has a later onset and milder clinical course than autosomal recessive forms. However, delayed diagnosis may result in prolonged metabolic acidosis and severe growth impairment. Here we report the case of a Japanese boy with a de novo SLC4A1 (NM_000342.4):c.1765C > T (p.Arg589Cys) variant who presented with marked growth failure from 6 months of age and was diagnosed with AD-dRTA at 27 months. Because severe short stature was the predominant clinical feature, venous blood gas analysis was performed and revealed metabolic acidosis (pH 7.197, HCO3- 11.5 mmol/L). Additional investigations demonstrated hyperchloremia, hypokalemia, hypercalciuria, bilateral nephrocalcinosis, rickets, an inappropriately high urine pH, and a positive urinary anion gap. Targeted gene panel analysis using next-generation sequencing, followed by Sanger confirmation, established the genetic diagnosis. After initiation of alkali therapy, metabolic acidosis progressively improved; serum bicarbonate first reached the normal range at 9 months and remained within or close to the normal range thereafter. Radiographic improvement of rickets was observed within 3 months, before cholecalciferol supplementation was initiated, and substantial catch-up growth occurred during 5 years of follow-up, with the height standard deviation score improving from - 4.1 to - 2.3, while renal function remained preserved. Prolonged auxological and biochemical follow-up of early-onset SLC4A1-associated AD-dRTA has rarely been reported. This case illustrates that AD-dRTA may present during infancy and that assessment of acid-base status may facilitate timely diagnosis in children with otherwise unexplained growth failure.