In the same report, an 11-yearold girl with asymptomatic microscopic hematuria and low serum urate was a compound heterozygote for W258X/R477H. Her mother had a heterozygous W258X mutation associated with renal hypouricaemia. In addition, a 15 year old girl with haematuria, proteinuria and renal hypouricaemia was noted to have a single heterozygous W258X mutation, whilst a 36-year-old female, with recurrent Cycloheximide 66-81-9 episodes of uric acid stones in the right ureter had a serum uric acid of 1.8 mg/dL and an elevated FEurate of 28.1%. She was heterozygote for a R90H variant in URAT1. Va´zquezMellado et al. reported patients heterozygous for C850G in URAT1 with primary gout and low serum uric acid concentrations whilst Ichida, et al. reported 5 individuals with a W258X heterozygous change, one of whom had a history of acute kidney injury and renal stones. Recently, the GLUT9 glucose transporter, encoded by SLC2A9 gene has been shown to have an important functional role in transporting uric acid from the renal tubular cells through the basolateral membrane into interstitium. Two additional reports have confirmed this finding. Matsuo et al. detected two heterozygous mutations in GLUT9 in two hypouricaemic subjects whom were negative for URAT1 mutations and confirmed their reduced transport activity in Xenopus oocyte expression system whilst Dinour et al. recently described two families with recessively inherited hypouricaemia who were negative for URAT1 mutations. Among hypouricaemic subjects in both families, three subjects had nephrolithiasis and three subjects had a history of exercise induced acute kidney injury. In these families, homozygous carriers of SLC2A9 mutations had very low serum levels of uric acid and extremely high values of FEurate. In this report we present combined data from Macedonian and English patients who are heterozygous carriers of SLC22A12 sequence variants. Although the presentations of the patients were varied, a systematic search for hypouricaemia identified patients with possible hereditary renal hypouricaemia and who are suitable for mutational analysis of SLC22A12 and SLC2A9 genes to try and identify abnormalities in the encoded urate transporters URAT1 and GLUT9, respectively. We identified seven patients harboring five SLC22A12 variants. Interestingly, three Macedonian patients carried mutations at amino acid position 434 of URAT1. Some of these variants in SLC22A12 were discovered following significant clinical episodes including nephrolithiasis in patients SK-1, NC-1 and NC-2. There were however, no episodes of exercise induced acute kidney injury that we are aware of. The sequence variant R434H was identified in one of our patients with hypouricaemia. This variant has a reported heterozygosity index of 0.011, although this variant was not detected in our normal control subjects. Additional studies are required to demonstrate whether this variant is a common cause of hypouricaemia. Of note, in our cohort of patients, we found no novel sequence variants in the GLUT9 transporter, leaving a number of patients with unexplained hypouricaemia. However, given the complexity of proximal tubule urate handling, other urate transporter protein variants may account for hypouricaemia in the remaining patients.