Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome

Article Article scientifique Article Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome eng 2010 author Harambat Jerome author Fargue Sonia author Acquaviva Cecile author Gagnadoux Marie-France author Janssen Francoise author Liutkus Aurelia author Mourani Chebl author Macher Marie-Alice author Abramowicz Daniel author Legendre Christophe author Durrbach Antoine author Tsimaratos Michel 133795 author Nivet Hubert author Girardin Eric 25598 author Schott Anne-Marie author Rolland Marie-Odile author Cochat Pierre 443-449 10.1038/ki.2009.435 20016466 0085-2538 http://www.nature.com/ki/journal/v77/n5/pdf/ki2009435a.pdf We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation. Amino Acid Substitution Arginine/metabolism Child Child, Preschool Cohort Studies Genotype Heterozygote Homozygote Humans Hyperoxaluria, Primary/diagnosis/*genetics Infant Kidney Failure, Chronic/genetics Mutation Phenotype Prognosis Retrospective Studies Transaminases/*genetics Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false 146 Pathogénèse du syndrome néphrotique idiopathique de l'enfant 180 Kidney international 77 5 30a5295b-422d-41a0-aed3-8a26d8e6fee7 Article Restricted file1.pdf 266624 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome	Kidney international			2010	705	0

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Tsimaratos, Michel