Phenylketonuria (PKU)

Summary

Phenylketonuria (PKU) is an autosomal recessive disorder affecting the metabolism of phenylalanine, leading to high levels of phenyl ketones in urine. The condition arises from a defect in phenylalanine hydroxylase, the enzyme converting phenylalanine to tyrosine. Untreated, PKU can cause severe brain development issues and low IQ. Early diagnosis and a lifelong diet limiting phenylalanine intake can prevent these complications, allowing affected individuals to lead normal lives.

Takeaways

• 🧬 Phenylketonuria (PKU) is an autosomal recessive disease affecting the metabolism of the amino acid phenylalanine.
• 🥚 Phenylalanine is an amino acid derived from dietary protein, with 25% used for new protein synthesis and 75% converted to tyrosine in the liver.
• 🌀 Tyrosine, produced from phenylalanine, is further metabolized into acetyl acetate and fumarate, which are then transformed into ketone bodies and glucose for energy.
• 🚫 PKU is characterized by high levels of phenyl ketones, or phenyl pyruvate, in the urine due to a block in phenylalanine metabolism.
• 🔬 The enzyme responsible for converting phenylalanine to tyrosine is phenylalanine hydroxylase, which requires the cofactor tetrahydrobiopterin.
• 🛑 A defect in phenylalanine hydroxylase or the inability to produce tetrahydrobiopterin leads to the accumulation of phenylalanine and the development of PKU.
• 🧬 PKU is inherited as an autosomal recessive trait, meaning an individual must inherit two defective genes, one from each parent, to exhibit symptoms.
• 🧠 Elevated phenylalanine levels can impair neuron myelination, leading to brain development issues and lower IQs in untreated individuals.
• 💀 Without treatment, PKU can be fatal, with half of untreated patients dying before age 20 and 75% before age 30.
• 🍼 Early diagnosis and treatment of PKU, including a lifelong restricted diet low in phenylalanine, can allow individuals to develop normally.
• 🩸 PKU can be diagnosed in infants by measuring phenylalanine levels in blood samples, which are significantly higher in affected individuals.

Q & A

What is phenylketonuria (PKU)?

Phenylketonuria, or PKU, is an autosomal recessive disease characterized by a problem with the enzyme involved in the metabolism of phenylalanine, leading to high levels of phenyl ketones in the urine.

How is phenylalanine normally metabolized in the body?

In normal individuals, phenylalanine from protein-rich food is broken down into individual amino acids. About 25% is used to build new proteins, while the remaining 75% is converted into tyrosine in the liver, which is further metabolized into acetyl acetate and fumarate for energy production.

What is the role of tyrosine in the body?

Tyrosine is an amino acid that, in addition to being used for protein synthesis, is metabolized into acetyl acetate and fumarate. Acetyl acetate is transformed into ketone bodies, and fumarate into glucose, both of which can be used by the body's cells for energy.

Why do patients with PKU have elevated levels of phenylalanine?

Patients with PKU have a defect in the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine. This defect leads to an accumulation of phenylalanine in the body.