Abstract
Phenylketonuria (PKU) is an inborn error of metabolism responsible for an accumulation of phenylalanine, which leads to cognitive and developmental disorders if left untreated. Most studies of adult PKU focus on neuropsychiatric complications, but new questions have been raised about systemic manifestations of PKU in adulthood. Fifteen adults with classic PKU with poor metabolic control and 15 matched healthy controls were recruited to compare their blood metabolomes by an untargeted multimodal approach (polar, apolar, and lipids) by LC/MS and a targeted approach to the tryptophan pathway. Targeted analysis revealed systemic serotonin hypometabolism and aberrant kynurenine metabolism, as well as potential implication of microbiota by differences in some indole compounds compared to controls. Untargeted analysis confirms previous findings regarding the TCA cycle, alanine aspartate glutamate metabolism, arginine and proline metabolism, and revealed some new metabolic perturbations such as arginine biosynthesis or glyoxylate and dicarboxylate metabolism. Future studies involving larger numbers of patients with varying degrees of metabolic control are needed to confirm these findings.