Phenylketonuria (PKU)

Phenylketonuria (PKU): Definition, Causes, Symptoms, and Management

Definition:

Phenylketonuria (PKU) is a rare genetic disorder in which the body cannot properly break down the amino acid phenylalanine due to a deficiency of the enzyme phenylalanine hydroxylase (PAH). This leads to a harmful buildup of phenylalanine in the blood, which can cause brain damage, intellectual disability, and other health problems if left untreated.

Causes of PKU

PKU is caused by mutations in the PAH gene, which provides instructions for producing the enzyme phenylalanine hydroxylase.

• In a healthy person: PAH converts phenylalanine (Phe) into tyrosine, which is used to make important neurotransmitters like dopamine.
• In a person with PKU: PAH is defective or absent, leading to an accumulation of excess phenylalanine, which becomes toxic to the brain and nervous system.

Genetic Inheritance

• PKU is an autosomal recessive disorder, meaning that a person must inherit two faulty copies of the PAH gene (one from each parent) to develop the condition.
• If a person inherits only one faulty gene, they are a carrier but do not have symptoms.

Symptoms of PKU

Untreated PKU (Severe Cases)

If phenylalanine levels are not controlled, symptoms may include:
🧠 Intellectual disability (if untreated from birth)
⚡ Seizures & neurological issues
😠 Behavioral problems (hyperactivity, aggression, anxiety)
👃 Musty odor (due to excess phenylalanine in sweat & urine)
🌱 Growth problems & developmental delays
🖤 Light skin, hair, and eyes (due to lack of melanin production, since phenylalanine is a precursor to melanin)
🤮 Vomiting & feeding difficulties in infants

Mild PKU or Well-Managed PKU

If treated early with a strict low-phenylalanine diet, individuals with PKU can have normal intelligence and development.

Types of PKU

1. Classic PKU (Most severe) – PAH enzyme is nearly absent, requiring strict lifelong management.
2. Moderate PKU – Some PAH activity remains, allowing for a slightly less restricted diet.
3. Mild PKU – More PAH activity, meaning individuals may tolerate higher phenylalanine intake.
4. Non-PKU Hyperphenylalaninemia (HyperPhe) – Mildly elevated phenylalanine levels but no major health risks.

Diagnosis of PKU

🩸 Newborn Screening (Heel-Prick Test) – All newborns in most countries are tested for PKU within the first few days of life.
🧬 Genetic Testing – Can confirm PAH gene mutations.
🩺 Blood Tests – Measure phenylalanine levels over time.

Treatment & Management of PKU

1. Low-Phenylalanine Diet 🍽️ (Lifelong)

Since phenylalanine is found in high-protein foods, individuals with PKU must strictly limit or avoid:
🚫 Meat, fish, eggs, dairy, soy, nuts, legumes
🚫 Artificial sweeteners (Aspartame, found in diet sodas and sugar-free products)

They can eat:
✅ Fruits, vegetables, low-protein grains
✅ Special PKU-friendly foods (low-protein breads, pasta, etc.)

2. Medical Formula (Phe-Free Protein Supplements) 🥤

• Since protein is essential, individuals with PKU take special medical formulas that provide protein without phenylalanine.
• These formulas contain tyrosine, which is needed for brain function.

3. Medications 💊

• Sapropterin (Kuvan) – A drug that helps some PKU patients break down phenylalanine better.
• Pegvaliase (Palynziq) – An enzyme therapy for adults with severe PKU.

4. Frequent Blood Monitoring 🩸

Patients must regularly check their blood phenylalanine levels to adjust their diet and treatment.

PKU and Pregnancy (Maternal PKU Syndrome)

👶 Pregnant women with PKU must strictly control phenylalanine levels, as high levels can cause:

• Intellectual disabilities in the baby
• Heart defects
• Growth restrictions

Can PKU Be Cured?

🔹 No cure currently exists, but strict dietary management and medical advancements allow individuals with PKU to live healthy lives. Gene therapy is being researched for a potential future cure.

Summary of PKU

Conclusion

PKU is a serious but manageable genetic disorder that affects the body’s ability to process phenylalanine. Early diagnosis and strict dietary management allow most individuals with PKU to live normal, healthy lives.