Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis

Area of Science:

• Pediatric Nephrology
• Medical Genetics
• Rare Genetic Disorders

Background:

• Primary distal renal tubular acidosis (dRTA) is a rare pediatric genetic disorder.
• Causative mutations identified in SLC4A1, ATP6V1B1, and ATP6V0A4 genes.
• Understanding genetic prevalence and phenotypic variation is critical for diagnosis and management.

Purpose of the Study:

• To analyze the prevalence and phenotypic differences of genetic mutations in children diagnosed with dRTA.
• To identify the most common causative genes in the Korean pediatric population.
• To correlate genotype with clinical presentation and long-term outcomes.

Main Methods:

• Genetic testing was performed on 17 children diagnosed with dRTA.
• Analysis included mutations in the three known causative genes: SLC4A1, ATP6V1B1, and ATP6V0A4.
• Clinical data including age of onset, metabolic acidosis severity, and long-term complications were collected.

Main Results:

• Pathogenic mutations were identified in 88.2% of patients, with six novel mutations found.
• SLC4A1 mutations were most prevalent (58.8%), followed by ATP6V0A4 (17.6%) and ATP6V1B1 (11.8%).
• SLC4A1 mutations were associated with later onset and less severe acidosis; ATP6V1B1 mutations correlated with sensorineural hearing loss. Nephrocalcinosis occurred in all patients. No genotype-phenotype correlation was observed for long-term prognosis.

Conclusions:

• SLC4A1 mutations are the predominant cause of dRTA in Korean children.
• Patients with SLC4A1 mutations experience a later disease onset and milder initial presentation.
• Long-term surveillance for hearing, renal function, and growth is essential for managing pediatric dRTA patients.