Phenylketonuria (PKU) is a rare, inherited metabolic disorder that affects the way the body processes phenylalanine, an essential amino acid found in many protein-rich foods. Without proper management, PKU can lead to severe brain damage, developmental delays, and lifelong neurological problems.
Although PKU is uncommon—affecting approximately 1 in 10,000–15,000 newborns worldwide—it’s one of the most well-known inborn errors of metabolism due to its serious consequences and the importance of early detection through newborn screening. The good news? With early diagnosis and a carefully controlled diet, individuals with PKU can lead healthy, normal lives.
Pathophysiology of PKU
PKU occurs because the body lacks enough of the enzyme phenylalanine hydroxylase (PAH), which is essential for converting phenylalanine into tyrosine.
Normal metabolism:Phenylalanine → (PAH enzyme + tetrahydrobiopterin) → Tyrosine → Neurotransmitters & hormones.
In PKU:
The absence or reduced activity of PAH means phenylalanine is not properly broken down, leading to:
- Phenylalanine accumulation in blood & tissues.
- Deficiency of tyrosine, which is important for neurotransmitter production.
This accumulation is toxic to the brain, especially during infancy and early childhood, when the brain is still developing rapidly.
Key Points:
- Amino acids from high-protein foods are essential for growth and development, but in PKU, they can become harmful if phenylalanine builds up.
- Brain damage can occur before birth if the mother has uncontrolled PKU during pregnancy.
.jpg "Phenylketonuria (PKU) – Causes, Symptoms, Diagnosis, Treatment & Diet")
Causes & Genetics
PKU is inherited in an autosomal recessive pattern:
- A child must inherit two defective PAH genes (one from each parent) to have PKU.
- Parents who carry one defective gene are healthy but are called carriers.
Genetic Counseling Tip:
If both parents are carriers, there’s a:
- 25% chance their child will have PKU.
- 50% chance their child will be a carrier.
- 25% chance their child will have no mutation.
This makes pre-pregnancy genetic counseling vital for at-risk couples.
Risk Factors
- Family history of PKU.
- Parents who are known PAH mutation carriers.
- Certain populations with higher prevalence (e.g., Northern European ancestry).
Signs & Symptoms of PKU
Newborns with PKU typically appear healthy at birth. However, without treatment, symptoms can develop within a few months.
Early symptoms include:
- Musty or mousy odor of breath, skin, or urine (due to phenylacetic acid).
- Irritability.
- Seizures.
- Eczema-like rash.
- Poor feeding.
- Vomiting.
Long-term complications (without treatment):
- Intellectual disability.
- Microcephaly (small head size).
- Hyperactivity.
- Behavioral problems.
- Psychiatric disorders.
Complications
If untreated, PKU can cause:
- Severe, irreversible intellectual disability.
- Seizures and neurological damage.
- Psychiatric issues (anxiety, depression).
- Social difficulties due to cognitive impairment.
PKU in Pregnancy – Maternal PKU Syndrome
A woman with PKU who becomes pregnant and has high phenylalanine levels can pass harmful levels to the fetus, even if the baby does not inherit PKU.
Possible fetal complications include:
- Intellectual disability.
- Microcephaly.
- Congenital heart defects.
- Low birth weight.
ATI Exam Tip:
Women with PKU should follow a low-phenylalanine diet for at least 3 months prior to conception to reduce fetal risk.
Diagnosis
PKU is typically detected through newborn screening within the first few days after birth.
Tests include:
- Guthrie bacterial inhibition assay (classic method).
- Tandem mass spectrometry (modern method to measure phenylalanine levels).
A phenylalanine level > 4 mg/dL in a newborn’s blood suggests PKU.
Management & Treatment
PKU treatment focuses on lifelong control of phenylalanine levels through diet and supplements.
1. Diet Therapy
Low-phenylalanine diet: Avoid foods high in protein such as:
- Meat, fish, poultry.
- Eggs.
- Dairy products.
- Soy products.
- Nuts, peanut butter.
Allowed foods:
- Fruits.
- Vegetables.
- Special low-protein breads & pastas.
Special infant formula (e.g., Lofenalac) is used instead of breast milk or regular formula to limit phenylalanine intake.
2. Tyrosine Supplementation
Since tyrosine becomes an essential amino acid in PKU, supplementation is important.
3. Sapropterin Dihydrochloride (BH4)
A medication that can help some PKU patients by enhancing residual PAH enzyme activity.
Dietary Table for PKU
| Allowed Foods | Avoid / Restricted Foods |
|---|---|
| Apples, bananas, berries | Meat, poultry, fish |
| Broccoli, carrots, spinach | Eggs |
| Special low-protein bread | Milk, cheese, yogurt |
| Rice, corn, oats (measured) | Soy products, tofu |
| Vegetable oils | Nuts, peanut butter |
NCLEX & Exam-Oriented Tips
- NCLEX: Low-phenylalanine diet, avoid high-protein foods, start treatment immediately after diagnosis.
- Kaplan: Avoid peanut butter & jelly sandwiches (high in protein).
- ATI: Avoid high-protein foods for at least 3 months prior to pregnancy in women with PKU.
Prognosis
With early detection and strict dietary management, children with PKU can achieve normal intelligence and development. However, even mild lapses in dietary control can cause subtle cognitive deficits.
Prevention
- Newborn screening is the best prevention method for complications.
- Carrier screening for couples with a family history.
- Preconception diet control for women with PKU.
FAQs on Phenylketonuria (PKU)
Q1: Can PKU be cured?
No, PKU cannot be cured, but it can be effectively managed with lifelong dietary restrictions.
Q2: Is breastfeeding allowed in PKU?
Yes, but only in controlled amounts under medical supervision, often combined with special PKU formula.
Q3: Can adults with PKU relax their diet?
No, lifelong dietary management is recommended to prevent neurological decline.
Q4: What happens if PKU is untreated?
Severe intellectual disability, seizures, and behavioral problems can develop.
Q5: Can PKU patients eat fruits and vegetables freely?
Most fruits and vegetables are allowed, but some higher-protein ones (like peas and corn) may need restriction.
