title: Acute kidney injury in two children caused by renal hypouricaemia type 2.
abstract: BACKGROUND
  Renal hypouricaemia is a heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (OMIM #220150), while type 2 is caused by defects in the SLC2A9 gene (OMIM #612076).
  
  
  METHODS
  The cases of two children, a 12- and a 14-year-old boy with acute kidney injury (proband 1: urea 9.4 mmol/l, creatinine 226 μmol/l; proband 2: urea 11.7 mmol/l, creatinine 202 μmol/l) are described. Both are offspring of nonconsanguineous couples in the UK. The concentrations of serum uric acid were consistently below the normal range (0.03 and 0.04 mmol/l) and expressed as an increase in the fractional excretion of uric acid (46 and 93 %).
  
  
  CONCLUSIONS
  A sequencing analysis of the coding region of uric acid transporters SLC22A12 and SLC2A9 was performed. Analysis of genomic DNA revealed two unpublished missense transitions, p.G216R and p.N333S in the SLC2A9 gene. No sequence variants in SLC22A12 were found. Our findings suggest that homozygous and/or compound heterozygous loss-of-function mutations p.G216R and p.N333S cause renal hypouricaemia via loss of uric acid absorption and do lead to acute kidney injury.
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Ke Karlovu 2, 128 53, Prague 2, Czech Republic. blanka.stiburkova@lf1.cuni.cz
authors.forename: Blanka
authors.initials: B
authors.lastname: Stiburkova
authors.forename: Judy
authors.initials: J
authors.lastname: Taylor
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Marinaki
authors.forename: Ivan
authors.initials: I
authors.lastname: Sebesta
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D002648:Child; D004252:DNA Mutational Analysis; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D015499:Renal Tubular Transport, Inborn Errors / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism; D014545:Urinary Calculi / Q000150:complications* / Q000235:genetics* / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid