Phenylketonuria was amongst the first of the metabolic disorders to be characterised, exhibiting an inborn error in
phenylalanine metabolism due to a functional deficit of the
enzyme phenylalanine hydroxylase. It affects around 700,000 people around the globe. Mutations in the gene coding for hepatic
phenylalanine hydroxylase cause this deficiency resulting in elevated plasma
phenylalanine concentrations, leading to
cognitive impairment, neuromotor disorders and related behavioural symptoms. Inception of low
phenylalanine diet in the 1950s marked a revolution in the management of
phenylketonuria and has since been a vital
element of all therapeutic regimens. However, compliance to dietary
therapy has been found difficult and newer supplement approaches are being examined. The current development of gene therapy and
enzyme replacement
therapeutics may offer promising alternatives for the management of
phenylketonuria. This review outlines the pathological basis of
phenylketonuria, various treatment regimes, their associated challenges and the future prospects of each approach. Briefly, novel drug delivery systems which can potentially deliver therapeutic strategies in
phenylketonuria have been discussed.