Nutritional and Therapeutic Strategies in Paediatric Phenylketonuria: A Narrative Literature Review

Phenylketonuria (PKU) is an autosomal recessive disorder characterised by an inborn error of phenylalanine (Phe) metabolism. Such errors are attributed to pathogenic gene variants causing phenylalanine hydroxylase (PAH) deficiency, impairing the hydroxylation of phenylalanine to tyrosine in the Phe metabolic pathway. This defect leads to plasma Phe concentrations above the normal range. If untreated, hyperphenylalaninemia can adversely affect brain function, leading to severe intellectual disability and seizures. Since 1969, the newborn dried blood spot test has remained the main method of early screening and diagnosis for PKU. The primary therapeutic management is a lifelong phenylalanine-restricted diet with the aim to decrease plasma Phe levels. The recommended diet consists of avoidance of high-protein foods such as meat, fish, eggs and nuts, and can be supplemented with high protein medical formulas which are low in phenylalanine. Sapropterin, a synthetic version of the cofactor tetrahydrobiopterin, can also be used as a treatment option in patients with a milder phenotype. This oral medication aims to increase PAH activity, subsequently reducing blood Phe concentrations. Novel gene-editing techniques are now being explored as potential curative strategies for PKU, with preclinical studies showing promising results in correcting pathogenic phenylalanine hydroxylase variants. This non-systematic review synthesises current literature on the management of PKU, with a focus on dietary interventions and recommendations.