pku

Phenylketonuria (PKU) is a genetic metabolic disorder caused by deficiency or malfunction of the enzyme phenylalanine hydroxylase, which normally converts the amino acid phenylalanine to tyrosine. As a result, phenylalanine accumulates in the blood and tissues, while tyrosine levels may fall. If untreated, high phenylalanine can cause brain damage, leading to intellectual disability, developmental delays, seizures, behavioral problems, and microcephaly. Tyrosine becomes an essential amino acid for individuals with PKU.

PKU is inherited in an autosomal recessive pattern. It occurs in people who inherit two defective PAH gene copies, one from each parent. The condition is detected at different frequencies across populations, and newborn screening programs have been widely adopted to identify affected infants shortly after birth to prevent early brain injury.

Diagnosis typically involves newborn screening tests that measure phenylalanine levels in blood. If elevated, further testing including plasma amino acid analysis and PAH gene sequencing may be performed to confirm the diagnosis. Ongoing monitoring of phenylalanine levels is important throughout life, along with regular neurodevelopmental assessments.

Management centers on lifelong dietary control. The diet restricts natural protein and phenylalanine while providing specialized medical foods and formulas to meet nutritional needs. Tyrosine is often supplemented, given its reduced synthesis. Some patients respond to tetrahydrobiopterin (BH4) therapy, which can increase phenylalanine tolerance. A small number of adults with PKU may be treated with enzyme substitution therapy (pegvaliase) to lower phenylalanine levels. Lifelong follow-up with metabolic specialists is recommended to optimize outcomes and growth.

With early and sustained treatment, many individuals achieve normal development and quality of life, though dietary adherence remains a common challenge.