Describe the gene and protein defects in phenylketonuria (PKU). How are these defects connected to disease symptoms?

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1. Phenylketonuria (PKU) is a genetic disorder caused by a defect in the PAH gene, which encodes the enzyme phenylalanine hydroxylase.
2. Phenylalanine hydroxylase is responsible for converting the amino acid phenylalanine into tyrosine. In PKU, this enzyme is either absent or non-functional due to mutations in the PAH gene.
3. As a result, phenylalanine accumulates in the body because it cannot be converted into tyrosine. This accumulation is toxic, particularly to the brain.
4. The high levels of phenylalanine lead to various symptoms, including intellectual disability, developmental delays, and other neurological problems.
5. The connection between the gene defect and symptoms is that the lack of functional phenylalanine hydroxylase enzyme leads to the buildup of phenylalanine, which causes the observed symptoms in individuals with PKU.

Key Concepts

Phenylalanine Hydroxylase (PAH)

Phenylketonuria (PKU) is primarily caused by a defect in the phenylalanine hydroxylase (PAH) enzyme, which is responsible for converting the amino acid phenylalanine into tyrosine. When PAH is deficient or inactive due to genetic mutations, phenylalanine accumulates in the body, leading to toxic levels that can cause neurological damage and cognitive impairment.

Autosomal Recessive Inheritance

PKU is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to express the disease. Carriers, who possess only one mutated gene, typically do not show symptoms but can pass the mutation to their offspring, highlighting the importance of genetic counseling in affected families.

Dietary Management

The management of PKU primarily involves a strict low-phenylalanine diet, which helps prevent the accumulation of phenylalanine and mitigates symptoms. This dietary intervention is crucial for individuals with PKU, especially during early development, to avoid severe intellectual disability and other neurological issues associated with high phenylalanine levels.