Al membrane of the proximal tubules in the kidneys [1]. The human SLC2A9 gene encodes two isoforms of GLUT9, long and short, through the use of alternative promoters. GLUT9 is expressed in human kidney proximal tubule epithelial cells, in particular, GLUT9L might be localized to the basolateral side and GLUT9S to the apical membrane, as suggested by expression studies performed using the Madin-Darby canine kidney cells [9]. Dinour and coworkers speculated that UA efflux is mediated solely by GLUT9L on the basolateral side, whereas UA absorption from the tubular lumen is carried out not only by URAT1, but also by GLUT9S and possibly other apical transporters [10]. According to this hypothesis, in patients with RHUC1, loss-of-function of URAT1 should produce a partial UA absorption defect with a FE-UA of 40 to 90 , whereas loss-of-function of GLUT9, in RHUC2 patients, due to either homozygous or compound heterozygous mutations, should preclude UA absorption by all the apical transporters (including URAT1), through complete blocking of UA efflux, resulting in a total UA reabsorption defect with a FE-UA of >100 [10-12]. In patients with RHUC2, either heterozygous mutations [11,12] or compound heterozygous and/or homozygous mutations have been identified in SLC2A9 [6,7,10,13,14]. To date, in SLC2A9, a total of 12 mutations (9 missense/ nonsense, 1 small insertion, 1 gross insertion, and 1 gross deletion) are currently reported in the HGMD professional 2012.4. Heterozygous SLC2A9 mutations cause hypouricemia mainly via haploinsufficiency [11,12,15]. In a number of studies, homozygous PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28381880 and compound heterozygous lossof-function mutations have been found to cause severe hypouricemia (serum UA near 0), markedly higher renal excretion, and nephrolithiasis and EIARF in most patients described from different ethnic groups [6,7,10,13,14]. Very recently, it was demonstrated that homozygous and/or compound heterozygous mutations do not necessarily lead to severe hypouricemia and a FE-UA of >150 [7]. Here, we report a young Pakistani man with severe EIARF who required temporary hemodialysis and who presented with very low serum UA levels. The FE-UA was high (>150 ), confirming the clinical diagnosis of RHUC. The severe clinical Olumacostat glasaretil web manifestation of low UA and very high FE-UA were suggestive of RHUC2 secondary to compound heterozygous or homozygous mutationsin SLC2A9. Mutational analysis of the SLC22A12 and SLC2A9 genes revealed the presence of two previously described mutations in the GLUT9 transporter, one found only in heterozygosis and the other either in compound heterozygosis or homozygosis, allowing RHUC2 diagnosis and providing new insights into the genotypephenotype correlation in this disorder.Case presentation A 24-year-old Pakistani man presented to the emergency room of our hospital suffering from diffuse abdominal and bilateral loin pain, diarrhea, vomiting and fever which began three days after a cricket match. The laboratory tests revealed kidney failure (serum creatinine 5.8 mg/dl; reference range 0.5-1.2), and the patient was admitted to our department. The patient appeared alert without neurological deficits, his temperature was 38 , blood pressure was 146/75 mmHg, pulse was 72 beats per minute rhytmic and regular, respiratory rate was 16 breaths per minute. Complete laboratory tests confirmed acute renal failure (serum creatinine 6.3 mg/dl) with metabolic acidosis, hypokalemia and hyperphosphatemia. Urinalysis showed many UA crystals, mi.
