Phenylketonuria (PKU) is a rare, inherited metabolic disorder that affects the body’s ability to process the amino acid phenylalanine (Phe). This condition is present from birth and is classified as an inborn error of metabolism. Without proper management, the buildup of phenylalanine can lead to severe and irreversible neurological damage. Early identification and intervention are necessary to prevent the toxic effects of phenylalanine accumulation in the brain.
The Genetic and Metabolic Basis of PKU
Phenylketonuria is rooted in a genetic change that impairs a metabolic pathway. The disorder is caused by mutations in the PAH gene, which provides instructions for making the enzyme Phenylalanine Hydroxylase (PAH). This enzyme is primarily active in the liver, converting phenylalanine into the amino acid tyrosine.
When the PAH gene is mutated, the resulting Phenylalanine Hydroxylase enzyme is missing, deficient, or non-functional. This deficiency halts the normal metabolic process, causing phenylalanine from the diet to accumulate in the blood and subsequently the brain. Elevated levels of this neurotoxic amino acid interfere with normal brain development, potentially leading to significant intellectual and developmental disabilities if left untreated.
PKU follows an autosomal recessive pattern of inheritance, meaning a child must inherit a mutated PAH gene copy from both parents to develop the condition. A person who inherits only one copy of the mutated gene is considered a carrier and does not show symptoms. If two parents are both carriers, there is a 25% chance with each pregnancy that their child will inherit both mutated copies and be affected by PKU.
Detecting PKU Through Newborn Screening
Detecting PKU early is straightforward and represents a major public health success. Newborn screening programs, mandatory in all 50 U.S. states, identify PKU and other metabolic disorders shortly after birth. Testing is performed between 24 and 48 hours after the baby is born, once they have ingested protein from breast milk or formula, which is necessary for accurate results.
The procedure involves a simple heel prick to collect a few drops of blood, which are blotted onto a filter paper card. This dried blood spot sample is sent to a laboratory for analysis, often utilizing advanced techniques like tandem mass spectrometry. This technology precisely measures the concentration of phenylalanine in the infant’s blood.
A high phenylalanine level in the screening test indicates a probable diagnosis of PKU, necessitating further confirmatory blood and genetic testing. Treatment must be started within the first few weeks of life to prevent the neurodevelopmental effects of phenylalanine accumulation. Early detection ensures that affected infants begin specialized treatment before any irreversible damage occurs.
Managing PKU with Specialized Nutrition
Lifelong PKU management relies on a strict, carefully controlled, low-phenylalanine diet. Since phenylalanine is an essential amino acid found in nearly all natural protein sources, the diet requires severely restricting or eliminating high-protein foods. These foods include meat, dairy, eggs, fish, nuts, and legumes.
To provide necessary nutrients and protein for growth without excess phenylalanine, individuals must consume specialized metabolic formulas, often called medical foods. These formulas are phenylalanine-free and contain a balanced mixture of amino acids, vitamins, and minerals. The small amount of allowed natural protein must be strictly measured and tailored to the individual’s tolerance and age.
Management requires frequent monitoring of blood phenylalanine levels to ensure they remain within a safe range, especially during periods of rapid growth. A registered dietitian specializing in metabolic disorders calculates the daily phenylalanine allowance and guides food choices. These choices often include specially formulated low-protein foods like breads and pastas.
Adjunctive therapies, such as the medication sapropterin dihydrochloride, are available for some responsive patients. Sapropterin is a synthetic form of the PAH enzyme cofactor, which increases the enzyme’s residual activity and raises tolerance for dietary phenylalanine. While this drug can permit a more liberalized diet, it is used in conjunction with a phenylalanine-restricted diet and does not replace careful nutritional management.