Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare genetic disorder characterized by the inability of the body to break down an amino acid called phenylalanine (Phe). Phe is one of the building blocks of proteins and is found in many foods. In people with PKU, the enzyme responsible for breaking down Phe, phenylalanine hydroxylase, is either missing or not functioning properly.

Symptoms

The symptoms of PKU can vary depending on the severity of the condition and the level of Phe in the blood. If left untreated, PKU can cause a range of problems, including:

• Intellectual disability: High levels of Phe in the blood can damage the brain and lead to intellectual disability.
• Seizures: Some people with PKU may experience seizures due to the buildup of Phe in the brain.
• Behavioral problems: Children with untreated PKU may exhibit behavioral problems, such as hyperactivity, anxiety, and depression.
• Delayed speech and language development: High levels of Phe can affect speech and language development in children.
• Skin rashes: Some people with PKU may experience skin rashes or eczema due to the buildup of Phe in the body.
• Musty odor: People with PKU may have a musty or mouse-like odor due to the accumulation of phenylacetate, a byproduct of Phe metabolism.

Causes and Risk Factors

PKU is caused by a mutation in the PAH gene, which provides instructions for making the enzyme phenylalanine hydroxylase. This mutation leads to a deficiency or complete absence of the enzyme, resulting in the accumulation of Phe in the body.

Risk factors for PKU include:

• Family history: Having a family history of PKU increases the risk of developing the condition.
• Genetic mutations: Mutations in the PAH gene can be inherited from one or both parents.

Treatments

The primary treatment for PKU is a strict diet that limits the intake of Phe. This diet typically includes:

• Phe-free formulas: Specialized formulas that provide all the necessary nutrients without Phe.
• Low-Phe foods: Foods that are naturally low in Phe, such as fruits, vegetables, and some grains.
• Phe-restricted foods: Foods that contain Phe, but in limited amounts, such as lean meats and fish.

In addition to dietary restrictions, other treatments for PKU may include:

• Supplements: Vitamin and mineral supplements to ensure adequate nutrition.
• Medications: Medications such as sapropterin dihydrochloride (Kuvan) to help reduce Phe levels in the blood.
• Gene therapy: Researchers are exploring gene therapy as a potential treatment for PKU, which involves introducing a healthy copy of the PAH gene into the body to restore enzyme function.

Management and Monitoring

To manage PKU effectively, regular monitoring of Phe levels in the blood is essential. This typically involves:

• Blood tests: Regular blood tests to measure Phe levels and adjust the diet accordingly.
• Dietary counseling: Ongoing dietary counseling to ensure adherence to the Phe-restricted diet.
• Medical follow-up: Regular medical check-ups to monitor overall health and adjust treatment as needed.

With proper management and treatment, people with PKU can lead healthy and active lives. Early diagnosis and intervention are critical in preventing long-term complications and ensuring optimal outcomes.