Background: The phenotypic characteristics of idiopathic renal hypouricemia (IRH) include impaired renal uric acid reabsorption,
low serum uric acid levels, and severe complications such as exercise-induced acute renal failure (EIARF) and nephrolithiasis. IRH is increasingly reported to be associated with inactivating mutations in either SLC22A12 gene encoding the human urate acid transporter 1 (hURAT1) or SLC2A9 gene encoding glucose transporter 9 (GLUT9) in proximal
tubules. Mutations in hURAT1 or GLUT9 have not been reported in Taiwanese patients with IRH. Purpose: To investigate the phenotypic and genetic characteristics in Taiwanese patients with IRH. Patients: Six Taiwanese patients (5 males and 1 female, mean age 30±23 years) with hypouricemia (serum uric acid concentration < 2.3 mg/dL) and concomitant excessive renal uric acid excretion (FEUA > 10%) from fi ve unrelated families were enrolled. Their clinical symptoms and biochemical studies were recorded. Methods: Molecular analysis of both SLC22A12 and SLC2A9 genes was performed by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and direct sequencing. Results: Serum uric acid concentration was 1.16±0.23 mg/dl with a fractional excretion of uric acid of 61±12 %. Two male patients experienced exercise-induced acute renal failure requiring hemodialysis. None of them had nephrocalcinosis or
uric acid stone. Despite a negative mutation in SLC2A9, four novel SLC22A12 mutations (W120R, M215L, T217M and T467M) and one recurrent homozygous (R90H) mutations were identifi ed in fi ve patients. Conclusion: EIARF can develop in Taiwanese patients with IRH, and most of them are males. Mutations in SLC22A12 rather than SLC2A9 cause IRH in patients with FEUA < 100%. Other candidate genes need to be identifi ed for IRH patients without SLC22A12 and SLC2A9 gene mutations.