Phenylketonurics are individuals with Phenylketonuria (PKU), an inherited metabolic disorder. This condition arises because the body cannot properly process an amino acid called phenylalanine, which is a building block of protein found in most foods. When phenylalanine is not broken down, it accumulates in the blood and brain to potentially toxic levels. Lifelong management is necessary to prevent the health problems associated with the condition.
The Genetic Basis of Phenylketonuria
Phenylketonuria is a genetic disorder caused by mutations in the PAH gene on chromosome 12. This gene holds the instructions for creating an enzyme called phenylalanine hydroxylase. The primary function of this enzyme, which works mostly in the liver, is to convert phenylalanine into another amino acid, tyrosine. Tyrosine is then used by the body to produce neurotransmitters like dopamine and epinephrine.
When mutations are present on both copies of the PAH gene, the enzyme is either less efficient or completely nonfunctional. This defect prevents the proper conversion of phenylalanine to tyrosine, leading to its buildup in the body. The condition is inherited in an autosomal recessive pattern, meaning a child must receive a mutated copy of the PAH gene from each parent to develop PKU. If an individual inherits only one copy, they are a carrier but will not show symptoms.
Diagnosis and Untreated Symptoms
PKU is identified through standard newborn screening programs in many countries. A few days after birth, a blood sample is taken from the baby’s heel to test for several conditions, including PKU. This screening measures phenylalanine levels in the blood; if high, further tests are conducted to confirm the diagnosis. Early detection allows treatment to begin immediately, which is important for preventing long-term health issues.
If PKU is not diagnosed, high levels of phenylalanine become toxic to the brain, leading to severe consequences. Symptoms develop gradually, and an infant may show developmental delays. By their first year, signs can include intellectual disability, seizures, and behavioral problems. A characteristic musty odor in the breath, skin, or urine, caused by the excess phenylalanine, is also a common sign. Other physical symptoms can include lighter skin and hair color, eczema, and an unusually small head size (microcephaly).
Dietary Management and Lifestyle
The primary lifelong management for PKU is a strictly controlled low-phenylalanine diet. The diet restricts phenylalanine intake to prevent its accumulation while ensuring the body receives other necessary nutrients for growth and health. This requires avoiding high-protein foods, including:
- Meat, fish, and chicken
- Eggs and dairy products
- Nuts, seeds, and legumes
- Flour-based breads and pastas
To get the protein and nutrients needed, individuals with PKU rely on a special medical formula. This phenylalanine-free formula provides a balanced mix of amino acids, vitamins, and minerals, compensating for the restricted diet. The formula is a foundation of PKU management from infancy through adulthood and is adjusted based on age, growth, and individual phenylalanine tolerance.
Another aspect of dietary management is avoiding the artificial sweetener aspartame. When digested, aspartame converts into phenylalanine in the body, which is dangerous for someone with PKU. This sweetener is found in many diet sodas, sugar-free products, and some medications, requiring careful label-reading. People with PKU can consume most fruits and vegetables, as well as specific low-protein starches, fats, and sugars to meet their energy needs.
Medical Treatments and Monitoring
Living with PKU requires lifelong monitoring to ensure phenylalanine levels remain within a safe range. This is achieved through regular blood tests, often done by collecting a blood sample from a finger prick at home and sending it to a lab. Monitoring is most frequent during infancy, early childhood, and pregnancy to allow for timely adjustments to the management plan.
In addition to diet, the Food and Drug Administration (FDA) has approved medications that can help manage PKU in some individuals. One medication is sapropterin dihydrochloride, an oral drug that helps the faulty enzyme break down phenylalanine more effectively. This treatment is not effective for everyone and is often used in combination with the PKU diet.
Another treatment is pegvaliase-pqpz, an injectable enzyme therapy for adults whose phenylalanine levels are not adequately controlled by other treatments. This medication works by providing a substitute for the deficient enzyme to break down phenylalanine in the blood. These medical interventions are prescribed by specialists and are used in addition to the dietary strategy.
Maternal PKU and Family Planning
For women with PKU, planning for pregnancy is an important consideration. High phenylalanine levels in the mother’s blood can cross the placenta and harm the developing fetus, a condition known as Maternal PKU Syndrome. The baby may be born without PKU but can suffer from serious health consequences, including:
- A small head size
- Low birth weight
- Congenital heart defects
- Intellectual disability
To prevent these outcomes, women with PKU must adhere to a strict low-phenylalanine diet before and throughout pregnancy. Medical guidelines advise maintaining safe phenylalanine blood levels for at least three months prior to conception. Frequent blood tests are necessary to ensure these levels stay within the target range for the entire pregnancy.
With careful planning and adherence to their management plan, women with PKU can reduce the risks and have healthy pregnancies. This requires a collaborative effort between the woman, her family, and a specialized healthcare team. Prenatal care for women with PKU often includes ultrasounds to monitor the baby’s growth and a fetal echocardiogram to check for heart defects.