Phenylketonuria (PKU) Disease

Phenylketonuria (PKU)

• PKU is a rare metabolic disease caused by the accumulation of phenylalanine (Phe) to toxic levels in the blood and brain, leading to severe brain disorders.
• Phe is an essential amino acid, necessary for life, but it cannot be produced by the body and must be acquired through protein-rich foods.

Normal Function of Phenylalanine Hydroxylase

• In normal individuals, the enzyme phenylalanine hydroxylase converts Phe to tyrosine, which is then used to produce neurotransmitters essential for brain development and function.

PKU as an Autosomal Recessive Genetic Disorder

• PKU is caused by a genetic mutation affecting the phenylalanine hydroxylase enzyme, located on chromosome 12.
• Over 600 mutations have been described, leading to varying degrees of enzyme function.

Effects of PKU on the Brain

• Elevated Phe levels and reduced tyrosine levels can alter brain function by:
  • Occupying transporters, making it difficult for tyrosine and tryptophan to cross the blood-brain barrier
  • Reducing dopamine, norepinephrine, and serotonin levels, leading to abnormal brain development and intellectual disability

Testing and Diagnosis

• Newborn screening is typically done 24 hours after birth, measuring blood Phe levels through a simple laboratory test.
• If the screening test shows high Phe levels and low blood tyrosine, a different method is used to confirm the diagnosis.

Treatment Options

• First-line therapy for PKU is a low Phe diet, including:
  • Medical foods such as low or no Phe medical formulas and modified foods
  • Elimination of high protein foods like meat, fish, eggs, and dairy
  • Customized Phe intake with medical professionals according to individual needs
• Two FDA-approved pharmaceutical treatments are available:
  • Kuvan, a cofactor for phenylalanine hydroxylase, which helps improve the patient's innate PAH enzyme activity and increase Phe tolerance
  • Palynziq, an enzyme that metabolizes Phe, substituting for the defective phenylalanine hydroxylase enzyme, and can be used in adults with PKU

Learn about Phenylketonuria (PKU), a rare metabolic disease caused by the accumulation of the amino acid phenylalanine, its effects on the brain, and its relation to protein and amino acids.