title: Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity.
abstract: BACKGROUND
  Familial renal hypouricemia (RHUC) is a hereditary disease characterized by hypouricemia, high renal fractional excretion of uric acid (FE-UA) and can be complicated by acute kidney failure and nephrolithiasis. Loss-of-function mutations in the SLC22A12 gene cause renal hypouricemia type 1 (RHUC1), whereas renal hypouricemia type 2 (RHUC2) is caused by mutations in the SLC2A9 gene.
  
  
  METHODS
  We describe a 24-year-old Pakistani man who was admitted twice to our hospital for severe exercise-induced acute renal failure (EIARF), abdominal pain and fever; he had very low serum UA levels (0.2 mg/dl the first time and 0.09 mg/dl the second time) and high FE-UA (200% and 732% respectively), suggestive of RHUC. Mutational analyses of both urate transporters revealed a new compound heterozygosity for two distinct missense mutations in the SLC2A9 gene: p.Arg380Trp, already identified in heterozygosity, and p.Gly216Arg, previously found in homozygosity or compound heterozygosity in some RHUC2 patients. Compared with previously reported patients harbouring these mutations, our proband showed the highest FE-UA levels, suggesting that the combination of p.Arg380Trp and p.Gly216Arg mutations most severely affects the renal handling of UA.
  
  
  CONCLUSIONS
  The clinical and molecular findings from this patient and a review of the literature provide new insights into the genotype-phenotype correlation of this disorder, supporting the evidence of an autosomal recessive inheritance pattern for RHUC2. Further investigations into the functional properties of GLUT9, URAT1 and other urate transporters are required to assess their potential research and clinical implications.
authors.forename: Guido
authors.initials: G
authors.lastname: Jeannin
authors.forename: Nicola
authors.initials: N
authors.lastname: Chiarelli
authors.forename: Mario
authors.initials: M
authors.lastname: Gaggiotti
authors.forename: Marco
authors.initials: M
authors.lastname: Ritelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Maiorca
authors.forename: Stefano
authors.initials: S
authors.lastname: Quinzani
authors.forename: Federica
authors.initials: F
authors.lastname: Verzeletti
authors.forename: Stefano
authors.initials: S
authors.lastname: Possenti
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. colombi@med.unibs.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cancarini
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015444:Exercise; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D010154:Pakistan; D010641:Phenotype; D012008:Recurrence; D006435:Renal Dialysis; D015499:Renal Tubular Transport, Inborn Errors / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D014527:Uric Acid / Q000097:blood; D014545:Urinary Calculi / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D055815:Young Adult
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C411811:SLC2A9 protein, human; D014527:Uric Acid