Fig. 1: PAICS deficiency and accumulation de novo purine synthesis intermediates.

Glycineamide riboside (GAr), formylglycineamide riboside (FGAr), aminoimidazole riboside (AIr), carboxyaminoimidazole riboside (CAIr), sukcinylaminoimidazolecarboxamide riboside (SAICAr), aminoimidazolecarboxamide riboside (AICAr) and formylaminoimidazolecarboxamide riboside (FAICAr) were quantified in the plasma and urine of patients. Concentrations of all DNPS intermediates were significantly increased in patients´ urine compared to control samples. In plasma samples from affected individuals, concentrations of upstream intermediates were also significantly increased compared to control samples. Concentrations are shown in standardized boxplot graphs with box from the first to third quartiles, whiskers to minimum and maximum, and all data points are displayed (open circles for controls and triangles for patients). C1 denotes urine controls aged 6–9 years (n = 47), C2 denotes urine controls aged 1–3 years (n = 33), and C3 denotes plasma controls aged less than 16 years (n = 9). P1 and P2 represent patient cases 1 and 2, respectively. The levels of GAr and FAICAr in plasma were below the limit of detection (LOD) and therefore not shown. If only control samples are bellow LOD, this is indicated on the graph by ‘<LOD’. One-sample Wilcoxon signed-rank tests were calculated by GraphPad Prism software and p-values are shown: **** for P < 0.0001, ** for P < 0.01, and ns for P ≥ 0.05.