Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome.
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.
Harambat
Jérôme
J
Service de Pédiatrie, Centre de Référence des Maladies Rénales Rares du Sud-Ouest, Centre Hospitalier Universitaire, Bordeaux, France.
Fargue
Sonia
S
Acquaviva
Cécile
C
Gagnadoux
Marie-France
MF
Janssen
Françoise
F
Liutkus
Aurélia
A
Mourani
Chebl
C
Macher
Marie-Alice
MA
Abramowicz
Daniel
D
Legendre
Christophe
C
Durrbach
Antoine
A
Tsimaratos
Michel
M
Nivet
Hubert
H
Girardin
Eric
E
Schott
Anne-Marie
AM
Rolland
Marie-Odile
MO
Cochat
Pierre
P
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*
D001120:Arginine; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase