Treatment of AICA ribosiduria by suppression of de novo purine synthesis.

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.

Hepatorenal Tyrosinaemia: Impact of a Simplified Diet on Metabolic Control and Clinical Outcome.

Background: Tyrosinaemia type 1 is a rare inherited metabolic disease caused by an enzyme defect in the tyrosine degradation pathway. It is treated using nitisinone and a low-protein diet. In a workshop in 2013, a group of nutritional specialists from Germany, Switzerland and Austria agreed to advocate a simplified low-protein diet and to allow more natural protein intake in patients with tyrosinaemia type 1. This retrospective study evaluates the recommendations made at different treatment centers and their impact on clinical symptoms and metabolic control. Methods: For this multicenter study, questionnaires were sent to nine participating treatment centers to collect data on the general therapeutic approach and data of 47 individual patients treated by those centers. Results: Dietary simplification allocating food to 3 categories led to increased tyrosine and phenylalanine blood concentrations without weighing food. Phenylalanine levels were significantly higher in comparison to a strict dietary regimen whereas tyrosine levels in plasma did not change. Non-inferiority was shown for the simplification and liberalization of the diet. Compliance with dietary recommendations was higher using the simplified diet in comparison to the stricter approach. Age correlates negatively with compliance. Conclusions: Simplification of the diet with increased natural protein intake based on three categories of food may be implemented in the diet of patients with tyrosinaemia type 1 without significantly altering metabolic control. Patient compliance is strongly influencing tyrosine blood concentrations. A subsequent prospective study with a larger sample size is necessary to get a better insight into the effect of dietary recommendations on metabolic control.