title: A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome.
abstract: Renal hypouricemia (RHU) is an autosomal recessive hereditary disease characterized by impaired renal urate reabsorption and subsequent profound hypouricemia. There are two types of RHU, type 1 and type 2, caused by the loss-of-function mutation of SLC22A12 and SLC2A9 genes, respectively. RHU predisposes affected people to exercise-induced acute renal failure (EIARF), posterior reversible encephalopathy syndrome (PRES) and nephrolithiasis. A Chinese patient had experienced three episodes of EIARF and one episode of PRES. The investigations showed profound hypouricemia and significantly increased renal excretion of UA. Cranial magnetic resonance imaging showed communicating hydrocephalus. Renal biopsy displayed interlobular artery intimal thickening with reduction of lumen and acute tubulointerstitial injury. The mutational analysis revealed a homozygous splice-site mutation in the SLC2A9 gene encoding glucose transporter 9. The patient was diagnosed as RHU type 2 caused by a loss-of-function mutation of the SLC2A9 gene. Consequently, he was strictly prohibited from strenuous exercise. During the 5-year follow-up, EIARF and PRES never recurred. Strenuous exercise may induce systemic (including renal and cerebrovascular) vasoconstriction eventually resulting in EIARF and PRES in patients with RHU. To our knowledge, this is the first report of a homozygous splice-site mutation in the SLC2A9 gene, renal arteriolar chronic lesion, concurrence of RHU and communicating hydrocephalus.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Rd 88, Hangzhou, 31009, China.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Mou
authors.forename: Lan-ping
authors.initials: LP
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D001706:Biopsy; D002648:Child; D004252:DNA Mutational Analysis; D015444:Exercise; D020022:Genetic Predisposition to Disease; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D040941:Heredity; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D054038:Posterior Leukoencephalopathy Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011237:Predictive Value of Tests; D022821:RNA Splice Sites; D012008:Recurrence; D015499:Renal Tubular Transport, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors; D014545:Urinary Calculi / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D022821:RNA Splice Sites; C411811:SLC2A9 protein, human