Clinical phenotype, family segregation, and follow-up of pediatric distal renal tubular acidosis associated with a homozygous SLC4A1 p.G701D variant

Abstract Background We report a case of SLC4A1-related distal renal tubular acidosis (dRTA) in a child with marked skeletal deformities, confirmed by family segregation analysis, and describe the clinical features, genetic findings, and follow-up changes. Methods We retrospectively reviewed the clinical history, laboratory findings, imaging results, genetic testing data, family segregation results, treatment course, and follow-up findings of a child with recurrent hypokalemia, growth retardation, and bilateral lower-limb deformities. Relevant studies were also reviewed for comparison. Results The patient was a 5-year-old boy with recurrent hypokalemia and progressive bilateral lower-limb deformities. Laboratory tests showed persistent hypokalemia, hyperchloremic normal-anion-gap metabolic acidosis, impaired urinary acidification, and abnormalities of bone metabolism. Imaging demonstrated rickets-like changes in both lower limbs and renal medullary abnormalities. Trio whole-exome sequencing identified a homozygous SLC4A1 c.2102G > A (p.G701D) variant, which was classified as likely pathogenic according to ACMG criteria. Sanger sequencing showed that both parents were heterozygous carriers of the same variant, consistent with autosomal recessive inheritance. Based on the clinical and genetic findings, the patient was diagnosed with hereditary SLC4A1-related dRTA. Potassium supplementation and alkali therapy corrected the severe hypokalemia present at admission, and subsequent follow-up showed near-normal serum potassium levels. However, TCO2 remained below the normal range and hyperchloremia persisted, whereas vitamin D and inorganic phosphate levels improved during follow-up. Conclusions This case supports the SLC4A1 p.G701D variant as the main pathogenic finding underlying dRTA in this child. In children presenting with orthopedic manifestations associated with hypokalemia, growth delay, and deformities, an underlying renal tubular disorder should be considered. Early evaluation of electrolytes, acid-base status, and genetic findings, together with family segregation analysis and longitudinal follow-up, may improve diagnostic accuracy and clinical management in hereditary dRTA.