Phenylketonuria: Symptoms, Causes & Treatment

Phenylketonuria (PKU) is a rare genetic disorder. When untreated, it can cause delayed development, seizures, and a strong musty or mouse-like odor in the skin, sweat, and urine.

This condition is caused by mutations in a gene that alters the enzyme needed to convert the amino acid phenylalanine into tyrosine. As a result, phenylalanine builds up in the blood.

At high levels, phenylalanine is toxic to the body. Phenylketonuria has no cure, but it can be treated with a phenylalanine-restricted diet, medical formulas, and, in some cases, medication.

Phenylketonuria symptoms

The main symptoms of phenylketonuria are:

• Chronic eczema or skin rashes

• Vomiting

• Delayed growth

• Strong musty or mouse-like odor in the urine, skin, and sweat

• Hyperactivity

• Lighter skin, hair, and eyes than unaffected family members

• Seizures

• Speech and language delay

Other possible symptoms include tremors, spasticity and ataxia, microcephaly, intellectual disability, irritability, depression, anxiety, apathy, aggression, and sleep irregularities.

Children with phenylketonuria are usually born without symptoms and appear healthy during the first few months of life. However, if the condition is not detected and treated early, symptoms usually begin to appear between 3 and 8 months of age.

Phenylketonuria during pregnancy

Women with phenylketonuria who are planning a pregnancy should talk with an obstetrician about the risks associated with having high phenylalanine levels in their blood.

This is because high phenylalanine levels in the mother’s blood increase the risk of the baby being born with congenital heart defects, microcephaly, developmental delay, and intellectual disability, even if the baby did not inherit the altered gene for the condition.

Confirming a diagnosis

Phenylketonuria is diagnosed shortly after birth through newborn screening, which is typically performed within the first 24 to 48 hours of life.

If the screening result is abnormal, the doctor should order additional tests, such as blood tests to measure phenylalanine and tyrosine levels.

A definitive diagnosis is based on persistently elevated phenylalanine levels, usually along with normal or low tyrosine levels, according to the American College of Medical Genetics and Genomics.

Genetic testing may also be ordered to identify the specific mutation, support genetic counseling, and help guide treatment.

Children who were not diagnosed through newborn screening can still be diagnosed at any age if symptoms develop.

Cause of phenylketonuria

Phenylketonuria is caused by mutations in a gene that affects the function of phenylalanine hydroxylase, the enzyme responsible for converting the amino acid phenylalanine into tyrosine. Tyrosine is involved in several processes in the body.

Because of this change in phenylalanine hydroxylase activity, phenylalanine builds up in the blood and other tissues. This can damage the body, especially the nervous system.

Phenylketonuria is a genetic condition passed from parents to children. For a child to have the condition, they must inherit two altered genes, meaning both parents must either have the condition or carry the gene responsible for phenylketonuria.

Treatment options

Treatment for phenylketonuria includes:

1. PKU diet

Dietary recommendations for phenylketonuria include:

• Foods to avoid: aspartame sweetener, meat, poultry, fish, eggs, milk and dairy products, beans, lentils, chickpeas, peas, soy, nuts and seeds, and products made from these foods, as well as wheat, oats, barley, rye, sorghum, corn, chocolate, and chocolate-flavored drinks

• Foods to limit: potatoes, cassava, sweet potatoes, green beans, collard greens, rice, passion fruit, dried fruits, and tamarind, which should be weighed and carefully calculated by a registered dietitian

• Foods to eat: fruits and vegetables in general, except those listed above, as well as tapioca, cassava starch, sago, oils, sugars, and gummy candies

Because breast milk contains lower levels of phenylalanine and offers several benefits, breastfeeding is usually encouraged. It is typically combined with a phenylalanine-free medical formula, with intake carefully monitored and adjusted by a pediatrician or metabolic specialist.

2. Phenylalanine-free medical formula

Phenylalanine-free medical formulas are amino acid mixtures that help meet protein needs for normal growth and development.

They should also contain vitamins, minerals, and essential fatty acids that may be lacking in the diet, in amounts appropriate for the person’s age.

This formula is used on an ongoing basis. The recommended amount depends on the person’s age, weight, and phenylalanine tolerance, and it may supply up to 85% of their daily protein intake.

3. Medications

During pregnancy and in the months before conception, strict control of phenylalanine levels is essential, primarily through a low-phenylalanine diet.

Sapropterin dihydrochloride may be used in some women with phenylketonuria who are responsive to this medication, as it helps improve phenylalanine metabolism.

Its use may help maintain safe phenylalanine levels and reduce the risk of maternal phenylketonuria syndrome, helping protect the baby.

Does phenylketonuria have a cure?

Because phenylketonuria is a genetic condition, it has no cure. However, it can be treated and managed.

Early diagnosis and treatment can help prevent severe complications, allowing many children with PKU to have normal neurological development and life expectancy.