Fiche publication
Date publication
novembre 2020
Journal
Journal of inherited metabolic disease
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KUENTZ Paul
Tous les auteurs :
Ramond F, Rio M, Héron B, Imbard A, Marie S, Billiemaz K, Denommé-Pichon AS, Kuentz P, Ceballos I, Piraud M, Vincent MF, Touraine R
Lien Pubmed
Résumé
5-Amino-4-imidazolecarboxamide-ribosiduria (AICA)-ribosiduria is an exceedingly rare autosomal recessive condition resulting from the disruption of the bifunctional purine biosynthesis protein PURH (ATIC), which catalyzes the last two steps of de novo purine synthesis. It is characterized biochemically by the accumulation of AICA-riboside in urine. AICA-ribosiduria had been reported in only one individual, 15 years ago. In this article, we report three novel cases of AICA-ribosiduria from two independent families, with two novel pathogenic variants in ATIC. We also provide a clinical update on the first patient. Based on the phenotypic features shared by these four patients, we define AICA-ribosiduria as the syndromic association of severe-to-profound global neurodevelopmental impairment, severe visual impairment due to chorioretinal atrophy, ante-postnatal growth impairment, and severe scoliosis. Dysmorphic features were observed in all four cases, especially neonatal/infancy coarse facies with upturned nose. Early-onset epilepsy is frequent and can be pharmacoresistant. Less frequently observed features are aortic coarctation, chronic hepatic cytolysis, minor genital malformations, and nephrocalcinosis. Alteration of the transformylase activity of ATIC might result in a more severe impairment than the alteration of the cyclohydrolase activity. Data from literature points toward a cytotoxic mechanism of the accumulated AICA-riboside.
Mots clés
AICA-riboside, AICA-ribosiduria, AICAR, ATIC, clinical genetics, de novo purine biosynthesis, metabolic disease, rare disease
Référence
J Inherit Metab Dis. 2020 11;43(6):1254-1264
