Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9compound heterozygosityReportar como inadecuado

Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9compound heterozygosity - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 15:3

Clinical-Molecular Genetics and Cytogenetics


BackgroundFamilial 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 presentationWe 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.

ConclusionsThe 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.

KeywordsRenal hypouricemia Exercise-induced acute renal failure SLC2A9 mutations p.Arg380Trp p.Gly216Arg AbbreviationsCKDChronic kidney disease

EIARFExercise-induced acute renal failure

FE-UAFractional excretion of uric acid

RHUCRenal hypouricaemia

UAUric acid.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-15-3 contains supplementary material, which is available to authorized users.

Guido Jeannin, Nicola Chiarelli contributed equally to this work.

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Autor: Guido Jeannin - Nicola Chiarelli - Mario Gaggiotti - Marco Ritelli - Paolo Maiorca - Stefano Quinzani - Federica Verzeletti


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