Phenylketonuria (PKU) is a rare inherited metabolic disorder that affects how the body processes protein. It is characterized by the inability to properly break down an amino acid called phenylalanine. Amino acids are often called the “building blocks” of protein, which we consume through foods like meat and milk. In individuals with PKU, phenylalanine can accumulate in the blood and brain to harmful levels, requiring lifelong management to prevent serious health complications.
Genetic Causes and Inheritance
Phenylketonuria is caused by mutations in the PAH gene. This gene holds the instructions for creating an enzyme named phenylalanine hydroxylase. This enzyme converts phenylalanine into tyrosine, another amino acid. When the PAH gene is mutated, the resulting enzyme is either less efficient or completely nonfunctional.
Nerve cells in the brain are particularly sensitive to high levels of phenylalanine, which can cause significant brain damage if left untreated. The severity of PKU depends on how much, if any, enzyme activity remains. Classic PKU is the most severe form, where there is little to no enzyme function.
The condition is inherited in an autosomal recessive pattern. This means a child must inherit two copies of the mutated PAH gene—one from each parent—to develop PKU. The parents are carriers, meaning they have one copy of the mutated gene but do not show symptoms of the disorder. If both parents are carriers, there is a 25% chance with each pregnancy that the child will have PKU.
Diagnosis and Symptoms of Untreated PKU
PKU is most often diagnosed in the first few days of life through routine newborn screening. In many countries, this involves a heel prick test where a small blood sample is collected from the baby’s foot. This early detection is preventative, as infants with PKU show no signs of the disorder at birth.
Without treatment, the buildup of phenylalanine can lead to severe and irreversible brain damage. Symptoms of untreated PKU can include permanent intellectual disability, seizures, and delayed development. Behavioral issues such as frequent temper tantrums, episodes of self-harm, and psychiatric disorders are also common.
A distinct characteristic of unmanaged PKU is a musty or mouse-like odor in the breath, skin, or urine. Individuals may also have lighter skin, hair, and eyes than their family members because phenylalanine is involved in producing melanin, the pigment responsible for coloration. Skin conditions like eczema are also frequently observed.
Lifelong Dietary Management
The primary management for PKU involves a strictly controlled, low-phenylalanine diet that must be followed for life. The goal of the diet is to consume only the amount of phenylalanine necessary for normal growth and development without allowing excess levels to accumulate. For many adults with PKU, maintaining this diet helps with concentration and reaction time.
This specialized diet requires the elimination of high-protein foods. Regular flour, which is used to make most breads and pastas, is also not permitted. Foods that must be avoided include:
- Meat
- Fish
- Eggs
- Dairy products
- Nuts
- Seeds
- Beans
To get the necessary nutrients for health, individuals with PKU rely on a special medical formula. This formula provides all the amino acids found in protein except for phenylalanine. It is a synthetic protein source that supplies essential nutrients without the risk of phenylalanine buildup. The formula is fundamental to PKU management from infancy throughout adulthood.
Some foods are allowed in carefully measured quantities. Most fruits and vegetables are naturally low in phenylalanine and can be included in the diet. Specialized low-protein breads, pastas, and other products are also available to help add variety to meals. It is also necessary to avoid the artificial sweetener aspartame, as it contains phenylalanine.
Medical Treatments and Monitoring
While diet is the main approach, certain medical treatments can supplement dietary management for some individuals. One available medication is sapropterin dihydrochloride, which can help the body process phenylalanine. This treatment is effective for a subset of patients who have a milder form of PKU where the body still produces a small amount of the phenylalanine hydroxylase enzyme.
For adults with PKU who have difficulty managing their blood phenylalanine levels with diet alone, an enzyme therapy called pegvaliase-pqpz may be an option. This injectable medication works by breaking down phenylalanine in the blood.
Consistent monitoring is a fundamental part of managing PKU. Regular blood tests are required to measure the amount of phenylalanine in the blood. The frequency of these tests changes throughout a person’s life, being more frequent in childhood and during pregnancy. The results of these tests allow healthcare providers to make precise adjustments to the individual’s diet and treatment plan to ensure levels remain within a safe range.
Maternal PKU and Long-Term Outlook
Maternal PKU refers to the risks associated with pregnancy in women with the disorder. If a woman with PKU has high phenylalanine levels during pregnancy, it can have severe consequences for her developing fetus. The baby may be born with serious health issues, including heart problems, a small head (microcephaly), and low birth weight, even if the baby does not inherit PKU.
To prevent these complications, women with PKU must maintain strict control of their blood phenylalanine levels before conception and throughout the entire pregnancy. This requires a highly restrictive diet and frequent monitoring to protect the health of the unborn child. Managing maternal PKU is an important aspect of lifelong care for women with the condition.
With early diagnosis and consistent management, the prognosis for individuals with PKU is excellent. People who adhere to their dietary and medical treatments can expect to lead full and healthy lives with normal cognitive development and life expectancy. The success of newborn screening programs has transformed the outlook for those born with this disorder.