title: Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome.
abstract: 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.
authors.affiliation: Service de Pédiatrie, Centre de Référence des Maladies Rénales Rares du Sud-Ouest, Centre Hospitalier Universitaire, Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Harambat
authors.forename: Sonia
authors.initials: S
authors.lastname: Fargue
authors.forename: Cécile
authors.initials: C
authors.lastname: Acquaviva
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gagnadoux
authors.forename: Françoise
authors.initials: F
authors.lastname: Janssen
authors.forename: Aurélia
authors.initials: A
authors.lastname: Liutkus
authors.forename: Chebl
authors.initials: C
authors.lastname: Mourani
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Macher
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Michel
authors.initials: M
authors.lastname: Tsimaratos
authors.forename: Hubert
authors.initials: H
authors.lastname: Nivet
authors.forename: Eric
authors.initials: E
authors.lastname: Girardin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schott
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Rolland
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
mesh_terms: D019943:Amino Acid Substitution; D001120:Arginine / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D007676:Kidney Failure, Chronic / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D000637:Transaminases / Q000235:genetics*
chemical_list: D001120:Arginine; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase