BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid (UA) reabsorption in the proximal tubule, is caused by mutations in SLC22A12 or SLC2A9. Most mutations have been identified in Japanese patients, and only a few have been detected in Europeans. METHODS: We report clinical, biochemical and genetics findings of fourteen Spanish patients, six Caucasians and eight of Roma ethnia, diagnosed with idiopathic RHUC. Two of the patients presented exercise-induced acute renal failure and another one had several episodes of nephrolithiasis and four of them had progressive deterioration of renal function, while the rest were asymptomatic. RESULTS: Molecular analysis revealed SLC22A12 mutations in ten of the patients, and SLC2A9 mutations in the other four. A new heterozygous SLC22A12 missense mutation, c.1427C>A (p.A476D), was identified in two affected members of the same family. The rest of the patients presented homozygous, heterozygous or compound heterozygous mutations that have been previously identified in patients with RHUC; SLC22A12 p.T467M and p.L415_G417del, and SLC2A9 p.T125M. Expression studies in Xenopus oocytes revealed that c.1427C>A reduced UA transport but did not alter the location of URAT1 protein on the plasma membrane. CONCLUSIONS: The biochemical and clinical features of our patients together with the genetic analysis results confirmed the diagnosis of RHUC. This is the first report describing SLC22A12 and SLC2A9 mutations in Spanish patients.

Department of Pathophysiology Tokyo University of Pharmacy and Life Sciences Tokyo Japan

Institute of Inherited Metabolic Disorders Charles University General University Hospital Prague Prague Czech Republic; Institute of Rheumatology Prague Czech Republic

Nefrología Pediátrica Hospital de Cruces Baracaldo Spain

Nefrología Pediátrica Hospital Infantil Niño Jesús Madrid Spain

Servicio de Nefrología Hospital General de Elche Spain

Servicio de Pediatría Hospital Infantil Miguel Servet Zaragoza Spain

Unidad de Investigación Hospital Nuestra Señora de Candelaria Santa Cruz de Tenerife Spain

Unidad de Nefrología Hemodialisis Hospital de Poniente Almeria Spain

Unidad de Nefrología Hospital Son Llàtzer Palma de Mallorca Spain

Unidad de Nefrología Pediátrica Hospital Materno Infantil Badajoz Spain

Unidad de Nefrología Pediatrica Hospital Nuestra Señora de Candelaria Santa Cruz de Tenerife Spain

References provided by Crossref.org

Analysis of Purine Metabolism to Elucidate the Pathogenesis of Acute Kidney Injury in Renal Hypouricemia

Functional Characterization of Rare Variants in OAT1/SLC22A6 and OAT3/SLC22A8 Urate Transporters Identified in a Gout and Hyperuricemia Cohort

Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population

Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal hypouricemia