Genetic Insights into Persistent Hypouricemia in Adults: Novel Findings from an Adult Nephrogenetic Clinic.

Introduction: Hypouricemia is an often-overlooked condition. Isolated persistent hypouricemia is rare and may be associated with uncommon genetic disorders, such as familial renal hypouricemia or xanthinuria. Methods: Fifteen non-consanguineous adult patients were included in this single-center study. Secondary causes of hypouricemia, including malnutrition, SIADH, cirrhosis, uricosuric drug use, and full-blown Fanconi syndrome, were excluded. Patients were classified as hyperuricosuric or hypouricosuric based on urinary uric acid levels. Clinical or whole-exome sequencing was performed, and variant pathogenicity was assessed using in silico prediction tools. Results: Ten patients were female (66.7%), and four were hypouricosuric (26.7%). Three patients (20%) had also glucosuria without diabetes mellitus and full-blown Fanconi syndrome. Thirteen patients (86.7%) carried at least one rare variant (variant of unknown significance, likely pathogenic, or pathogenic) in genes associated with hypouricemia: 1 patient with homozygous Conclusion: Our study expands the clinical and genetic spectrum of persistent hypouricemia. Genetic testing has a high diagnostic yield and should be considered in patients with unexplained persistent hypouricemia.