Phenylketonuria (PKU) and Amino Acids

Phenylketonuria (PKU)

• A rare metabolic disease that can lead to severe brain disorders due to the accumulation of the amino acid phenylalanine (Phe) to toxic levels in the blood and brain.
• Caused by the deficiency of the enzyme phenylalanine hydroxylase, which converts Phe to tyrosine.

Amino Acids and Phenylalanine

• Amino acids are the basic building blocks of proteins.
• Phenylalanine (Phe) is an essential amino acid, necessary for life, but cannot be produced by the human body.
• Phe must be acquired through foods that contain protein.

Normal Metabolism of Phenylalanine

• Normally, Phe is converted to tyrosine by the enzyme phenylalanine hydroxylase.
• Tyrosine is then converted into neurotransmitters essential for normal brain development and function.

Genetic Disorder

• PKU is an autosomal recessive genetic disorder that affects the function of the phenylalanine hydroxylase enzyme.
• The phenylalanine hydroxylase gene is located on chromosome 12, with over 600 mutations described.

Symptoms of PKU

• Untreated, people with PKU develop symptoms such as severe intellectual disability, psychiatric disorders, and seizures.

Maternal PKU Syndrome

• A pregnant woman with PKU must pay special attention to her Phe levels to reduce the risk of Maternal PKU Syndrome.
• Maternal PKU Syndrome can result in heart defects, microcephaly, and developmental disability in the baby.

Effect of Elevated Phe Levels on Brain Function

• Elevated Phe levels and reduced tyrosine levels can change the way the brain functions.
• Phe occupies the same transporters as tyrosine and tryptophan, reducing their levels in the brain.
• This leads to decreased levels of dopamine, norepinephrine, and serotonin, resulting in abnormal brain development and intellectual disability.

Diagnosis and Treatment

• Testing for PKU is typically done as part of routine newborn screening approximately 24 hours after birth.
• First-line therapy for PKU is the low Phe diet, which includes medical foods and modified foods to restrict Phe intake.
• Patients must customize their Phe dietary intake with medical professionals according to their individual needs.