10 Questions
What is the primary function of the enzyme phenylalanine hydroxylase?
To convert phenylalanine into tyrosine
What is the consequence of elevated phenylalanine levels in the brain?
Altered brain function and potential intellectual disability
Why is it essential for individuals with PKU to monitor their phenylalanine intake?
To prevent the buildup of toxic levels of phenylalanine in the blood and brain
What is the relationship between phenylalanine and tyrosine in the brain?
Phenylalanine is converted into tyrosine by the enzyme phenylalanine hydroxylase
What is the genetic characteristic of PKU?
Autosomal recessive genetic disorder
What is the primary consequence of elevated Phe levels in the bloodstream?
Impaired synthesis of tyrosine and tryptophan
What is the primary purpose of Kuvan in the treatment of PKU?
To increase the patient's innate PAH enzyme activity
What is the primary difference between Palynziq and Kuvan?
Palynziq substitutes for the defective enzyme, while Kuvan increases PAH activity
What is the primary goal of the low Phe diet in the treatment of PKU?
To reduce the intake of dietary natural protein
What is the primary consequence of untreated PKU?
Severe seizures and developmental delay
Study Notes
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.
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