Phenylketonuria (PKU) is a rare inherited disorder that impacts the body’s ability to process a specific amino acid called phenylalanine. This amino acid, a protein building block, is found in many foods, including meat, eggs, nuts, milk, and some artificial sweeteners. Without proper processing, phenylalanine can build up to harmful levels in the body, leading to serious health issues.
The Genetic Roots of PKU
The underlying cause of PKU is a mutation in the PAH gene. This gene provides the blueprint for phenylalanine hydroxylase (PAH). The PAH enzyme converts phenylalanine into tyrosine, a process requiring tetrahydrobiopterin (BH4).
When a mutation occurs in the PAH gene, the body produces an altered or no functional enzyme. This deficiency means phenylalanine cannot be properly broken down, leading to its accumulation in the blood and other tissues. Nerve cells in the brain are sensitive to elevated phenylalanine levels, and excessive amounts can cause damage.
PKU follows an autosomal recessive inheritance pattern. This means that a child must inherit two copies of the mutated PAH gene, one from each parent, to develop the condition. If a child receives only one copy, they become a carrier and typically do not exhibit symptoms. If both parents are carriers, there is a one in four chance their child will inherit PKU with each pregnancy.
Detecting PKU
Early identification of PKU prevents serious health complications. Newborn screening is the primary method for detecting this condition shortly after birth. This routine screening, performed in all U.S. states, often involves a heel prick to collect a few drops of blood.
The blood sample is sent to a laboratory for analysis, typically within 24 hours to seven days after birth. This test measures the level of phenylalanine in the baby’s blood. A phenylalanine level exceeding 4 milligrams per deciliter (mg/dL) is considered high and may indicate PKU, while normal levels are generally less than 2 mg/dL.
If the initial newborn screening results suggest PKU, confirmatory diagnostic tests are performed. These may include additional blood tests to precisely measure phenylalanine levels and genetic testing to pinpoint the specific PAH gene mutations responsible for the condition. Early detection allows for prompt intervention, preventing long-term complications.
Managing PKU
Managing PKU involves a strict, lifelong low-phenylalanine diet. This dietary approach carefully controls the intake of protein-rich foods such as meat, dairy, nuts, and certain grains, as these contain phenylalanine. Individuals with PKU also need to avoid artificial sweeteners like aspartame, which are high in phenylalanine.
Special medical formulas and supplements are a necessary part of this dietary management. These phenylalanine-free protein substitutes provide necessary amino acids, essential fatty acids, and other micronutrients restricted in a low-phenylalanine diet. The amount of phenylalanine an individual can safely consume varies for each person.
Some individuals with PKU may benefit from medical treatments in addition to dietary management. Sapropterin dihydrochloride (Kuvan) is a synthetic form of tetrahydrobiopterin (BH4), a cofactor for the PAH enzyme. This medication can help some patients with milder or moderate forms of PKU by enhancing the activity of any remaining functional PAH enzyme, potentially allowing for a less restrictive diet. Ongoing research explores advanced therapies like enzyme replacement therapy (e.g., pegvaliase), which converts phenylalanine to other compounds. Gene therapy is also being investigated.
Long-Term Outlook
With early diagnosis and consistent adherence to treatment, individuals with PKU can generally lead healthy lives with typical cognitive development. Early intervention, especially through dietary management, has improved outcomes, allowing most individuals to avoid the severe intellectual disability seen in untreated cases. Consistent treatment throughout life optimizes cognitive and psychiatric well-being.
Despite good treatment adherence, some individuals may still experience subtle cognitive challenges, such as difficulties with processing speed or executive functions like attention. If treatment is not consistently followed, especially during childhood and adolescence, elevated phenylalanine levels can lead to neurological problems, developmental delays, behavioral issues, and psychiatric symptoms like anxiety or depression. Lifelong adherence to the dietary regimen and other prescribed treatments minimizes these potential challenges and supports overall health.