Improving Detection of Hereditary Renal Hypouricemia and Genotype-Phenotype Correlation: A Retrospective Observational Study

P. Fortes González, A. URISARRI RUIZ DE CORTÁZAR, N. CARRERA CACHAZA, E. SÁNCHEZ CAZORLA, M. GARCÍA MURIAS, A. BARCIA DE LA IGLESIA, C. DIAZ RODRÍGUEZ, M. GARCÍA GONZÁLEZ

Hereditary renal hypouricaemia is a genetic disorder caused by impaired renal reabsorption of uric acid (UA), leading to low serum UA (SUA) and high fractional excretion (FEUA). Although often asymptomatic, it is likely underdiagnosed and may cause severe complications. We evaluated four biomarkers (SUA, FEUA, SUA–FEUA ratio and SUA²) in a local cohort and a European validation cohort, and analysed genotype–phenotype correlations using published data. Confirmed cases included biochemical phenotypes outside classic thresholds, and some patients without identified variants showed case‑like profiles. All biomarkers except FEUA distinguished cases from controls with 100% sensitivity and ≥90% specificity, particularly with a SUA threshold ≥3 mg/dL. European heterozygous SLC2A9 carriers showed more adverse UA profiles than non‑European carriers, suggesting genetic background effects. Broader screening with higher SUA cut‑offs may reduce false negatives and improve prevention complications.

Keywords: Diagnosis Sensitivity Genetics

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