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

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.