Julien H Park 1, Ulrike Och 1, Tim Braun 2, Matthias F Kriegel 3, Saskia Biskup 4, Herbert Korall 2, Constantin E Uhlig 3, Thorsten Marquardt 5
Abstract
AICA ribosiduria is an ultra-rare disorder of de novo purine biosynthesis associated with developmental delay of varying severity, seizures, and varying degrees of visual impairment due to chorioretinal atrophy. Caused by biallelic pathogenic variants in ATIC, accumulation of AICA-riboside is the biochemical hallmark and presumed pathomechanism of the condition. In this study, we report the case of a teenage patient compound-heterozygous for the variants c.1277 A > G (p.K426R) and c.642G > C (p.Q214H) in ATIC, with the latter not previously reported. Excessive secretion of AICA-riboside and succinyladenosine was significantly reduced following the introduction of a purine-enriched diet. By suppressing de novo purine biosynthesis in favour of purine salvage, exogenous purine substitution represents a promising treatment approach for AICA ribosiduria. SYNOPSIS: Suppression of de novo purine biosynthesis by increased exogeneous purine supply leads to decreased accumulation of AICA-riboside and succinyl-adenosine and thus is a promising treatment approach for AICA ribosiduria.
Keywords: AICA riboside; AICA ribosiduria; Purine; Purine metabolism.
- Department of General Pediatrics, University of Münster, Münster, Germany.
- Zentrum für Stoffwechseldiagnostik GmbH, Reutlingen, Germany.
- Department of Ophthalmology, University of Münster Medical Centre, Münster, Germany.
- Center for Genomics and Transcriptomics CeGaT GmbH and Praxis für Humangenetik Tübingen, Tübingen, Germany.
- Department of General Pediatrics, University of Münster, Münster, Germany. Electronic address: marquat@uni-muenster.de.