Metabolic Crisis: Phenylketonuria

Phenylketonuria (PKU) is a congenital disease caused by impaired phenylalanine (Phe) metabolism. It has a prevalence of around 1 in 24,000 people worldwide. It occurs due to a mutation in the phenylalanine hydroxylase enzyme. It leads to disruption of Phe metabolism. Newborns with PKU may appear normal earlier. However, if untreated, later on, symptoms develop and may include foul-smelling breath, sweat, or urine. Excessive accumulation of Phe in the brain leads to brain dysfunction, which may lead to epilepsy, intellectual impairment, and cognitive disorders in adulthood. Metabolic acidosis of PKU leads to osteopenia. The patient’s and family’s quality of life also deteriorates in the long run. Diet management has always been the main bastion of PKU. However, a lack of adherence to the diet led to failure. Enzyme therapy, enzyme substitution, and gene therapy proved to be promising in nature.