Phenylketonuria (PKU)

Phenylketonuria (PKU) is an inherited metabolic disorder that prevents the body from being able to break down the amino acid phenylalanine. If children born with PKU are not treated, phenylalanine in the blood can rise to levels that are harmful to the brain, interfering with brain development and causing intellectual disability.

Fortunately, PKU is highly treatable with diet and/or medication. Following the prescribed treatment for PKU is a lifelong endeavor that requires support from family and your health care team. Children and adults who follow their treatment regimen can live full, active lives.

PKU is a genetic condition affecting about one in 15,000 babies born in the United States. People born with PKU lack phenylalanine hydroxylase (PAH), the enzyme needed to break down phenylalanine (“phe”), an amino acid found in virtually all protein foods. When phe is not broken down, it builds up in the blood and brain.

If not treated during infancy and childhood, PKU can cause developmental delay and intellectual disability. However, children who start PKU treatment as newborns and continue through childhood are expected to have normal growth and development.

Those who stop treatment later in childhood or as adults may develop cognitive and mental health symptoms, including attention deficits, mood-related issues, poor self-control, reduced ability to plan and prioritize tasks, and brain “fog.” However, these symptoms can be at least partly reversed by going back on treatment.

PKU is usually identified by newborn screening (a heel-stick blood test), which is now required in all 50 states. It was the first condition to be screened for when newborn testing began in the 1960s.

PKU requires lifelong care, starting within the week or two after birth. The cornerstone of treatment is a specially prescribed diet that has very low levels of phenylalanine (phe). Because phe is found in nearly all proteins, the diet may limit or exclude meat, eggs, dairy products, legumes, and many grains. Many patients consume specially formulated low-protein foods and drink nutritional formulas.

Several medications can reduce or even eliminate the need for dietary treatment. These include:

• Sapropterin (Kuvan), a vitamin cofactor that helps the body break down phe.
• Phenylalanine ammonia lyase (PAL), a replacement enzyme that also breaks down phe. Approved in 2018 for adults with PKU, it is formulated as pegvaliase (Palynziq) and injected daily under the skin.

Other treatments are being studied but are not yet available.

The Dr. Harvey Levy Program for Phenylketonuria and Related Conditions at Boston Children’s Hospital grew out of Boston Children’s original PKU clinic, the first in the country. Today, as part of the Metabolism Program in the Division of Genetics and Genomics, we take a comprehensive approach to testing and treating children and adults with PKU, other amino acid disorders, and cofactor disorders.

Our dedicated team of physicians, dietitians, nurse practitioners, nurse, social workers, psychologists, and biochemical genetics laboratory specialists are committed to supporting people with this highly treatable condition. PKU requires lifelong care, and our multidisciplinary team will work with you to achieve the best health available.

We also run a special clinic, the PAL Clinic, for patients with PKU who are receiving enzyme substitution therapy.