Severe skeletal and renal complications in SLC4A1-related distal renal tubular acidosis following prolonged treatment interruption: a case report highlighting transition-related vulnerability

Abstract

Abstract Background SLC4A1-related distal renal tubular acidosis (dRTA), caused by dysfunction of the anion exchanger 1 (AE1), is typically associated with a relatively mild and late-onset phenotype. However, outcomes may vary substantially, particularly in the setting of delayed diagnosis or prolonged interruption of therapy. Case presentation We report a 31-year-old woman with genetically confirmed SLC4A1-related dRTA who presented with recurrent nephrolithiasis, urinary tract infections, and severe skeletal deformities. She discontinued alkali therapy for approximately 13 years after childhood diagnosis, resulting in extreme growth retardation (height −6.2 SD) and advanced osteomalacia. Laboratory evaluation revealed severe hyperchloremic metabolic acidosis, hypokalemia, persistently alkaline urine, and mildly reduced renal function consistent with chronic kidney disease (CKD) stage 2. Imaging demonstrated Looser–Milkman pseudofractures, “fish vertebrae,” and nephrocalcinosis with ureteral obstruction requiring double-J stent placement. Genetic testing identified a heterozygous SLC4A1 variant (c.2704G>T, p. Asp902Tyr), classified as likely pathogenic. The patient’s mother, carrying the same variant, exhibited a milder phenotype. Conclusions This case illustrates that prolonged interruption of alkali therapy in SLC4A1-related dRTA may result in severe and irreversible skeletal and renal complications, even in genotypes typically considered mild. It highlights the pediatric-to-adult transition as a critical period for treatment discontinuation and underscores the importance of lifelong therapy, early intervention, and long-term follow-up.