Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity

BMC Medical Genetics

Giovanni Cancarini¹  Marina Colombi²  Stefano Possenti¹  Federica Verzeletti¹  Stefano Quinzani²  Paolo Maiorca¹  Marco Ritelli²  Mario Gaggiotti¹  Nicola Chiarelli²  Guido Jeannin¹ 

[1] Operative Unit of Nephrology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University Hospital Spedali Civili, Brescia, Italy;Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy

关键词: p.Gly216Arg;    p.Arg380Trp;    SLC2A9 mutations;    Exercise-induced acute renal failure;    Renal hypouricemia;   

Others  :  1122545
DOI  :  10.1186/1471-2350-15-3

 received in 2013-09-03, accepted in 2013-12-26,  发布年份 2014

【 摘 要 】

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.

Case presentation

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.

【 授权许可】

   
2014 Jeannin et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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