Phenylketonuria (PKU) is a rare genetic disorder that affects the body's ability to process an essential amino acid called phenylalanine. This condition is caused by a mutation in the gene responsible for producing an enzyme called phenylalanine hydroxylase (PAH). Without this enzyme, phenylalanine builds up to toxic levels in the blood and brain, leading to various health problems.
Genetic Mutation: The primary cause of PKU is a genetic mutation in the PAH gene. This gene provides instructions for making the PAH enzyme, which is responsible for converting phenylalanine into another amino acid called tyrosine. In individuals with PKU, the mutation impairs the production or function of the PAH enzyme, resulting in the accumulation of phenylalanine.
Autosomal Recessive Inheritance: PKU follows an autosomal recessive pattern of inheritance. This means that both parents must carry a copy of the mutated gene for their child to be affected. If both parents are carriers, there is a 25% chance with each pregnancy that their child will have PKU. If only one parent is a carrier, the child will be a carrier but not affected by the disorder.
Phenylalanine-Restricted Diet: Another important factor contributing to the development of PKU is the dietary intake of phenylalanine. Individuals with PKU lack the ability to break down phenylalanine effectively, leading to its accumulation in the body. Therefore, a phenylalanine-restricted diet is crucial in managing PKU. This diet involves avoiding high-protein foods, such as meat, fish, eggs, dairy products, nuts, and certain grains, as they are rich in phenylalanine. Instead, individuals with PKU consume specially formulated low-protein foods and medical supplements to meet their nutritional needs.
Untreated PKU: If left untreated, PKU can have severe consequences on an individual's health and development. The excessive levels of phenylalanine in the blood can cause intellectual disability, developmental delays, behavioral problems, seizures, and even psychiatric disorders. Therefore, early diagnosis through newborn screening programs and prompt initiation of treatment are crucial to prevent these complications.
New Mutations: In some cases, PKU can occur without a family history of the disorder. These cases are caused by new mutations in the PAH gene that arise spontaneously. These new mutations can be passed on to future generations if the affected individual has children.
Other Genetic Variants: While mutations in the PAH gene are the most common cause of PKU, there are rare cases where the disorder is caused by mutations in other genes involved in the production or recycling of tetrahydrobiopterin (BH4), a cofactor required for the PAH enzyme to function properly. These variants are known as BH4-responsive PKU or atypical PKU.
Environmental Factors: Although PKU is primarily a genetic disorder, certain environmental factors can influence its severity. For example, high temperatures, infections, stress, and other illnesses can temporarily increase phenylalanine levels in individuals with PKU, leading to symptoms such as irritability, poor concentration, and skin rashes. Additionally, pregnancy and hormonal changes can affect phenylalanine metabolism in women with PKU.
Conclusion: Phenylketonuria is primarily caused by genetic mutations in the PAH gene, resulting in the deficiency of the phenylalanine hydroxylase enzyme. This leads to the accumulation of phenylalanine in the body, which can have detrimental effects on an individual's health and development. Early diagnosis, newborn screening, and adherence to a phenylalanine-restricted diet are essential in managing PKU and preventing its associated complications.