Phe-restricted diets have been the basis of therapy for phenylketonurics; however, little is known how this treatment effects homeostasis of other important amino acids. This study aimed to describe blood amino acid patterns in neonates with phenylketonuria (PKU) and identify any effects of Phe restriction on these patterns in young children.
Neonate group (age 0–4 weeks): 45 PKU patients, 45 age-/sex-matched controls without PKU; 1–4 year-old group: 27 diet-treated PKU patients, 27 age-/sex-matched children without PKU. Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) performed on dried blood spots.
Elevated blood phenylalanine (Phe), arginine (Arg), citrulline (Cit), valine (Val) and methionine (Met) concentrations were observed in PKU neonates relative to controls (Phe, Arg, Cit, Val: P < 0.001; Met: P < 0.05), of which Phe, Arg, and Met levels could be either partially or completely restored with dietary intervention. Diet had no effect on elevated Cit and Val. Decreased blood tyrosine (Tyr) and proline (Pro) concentrations were observed in PKU neonates compared to controls (P < 0.001). Both amino acids could be near completely restored to normal with dietary treatment. No significant differences in alanine (Ala), leucine (Leu), ornithine (Orn) and glycine (Gly) concentrations were found in the PKU neonates and 1–4 year-old groups (P > 0.05).
Blood amino acid homeostasis is disrupted in neonates and young children with PKU. Although dietary intervention adjusts amino acid homeostasis in the direction of a healthy equilibrium, complete restoration is not achieved. This persistent disruption may represent a clinically significant barrier to achieving the best possible therapy for those with PKU. Use of laboratory technologies such as LC-MS/MS enable characterization of persistent blood amino acid disequilibrium in the treated phenylketonuric. Testing of this kind presents opportunity for customized treatment feedback that may allow even greater optimization of therapy for neonates and children with PKU.