Phenylketonuria is caused by how? It is an autosomal recessive genetic disease, mainly due to a mutation in the phenylalanine hydroxylase gene, which leads to a reduction in the activity of phenylalanine hydroxylase. Phenylalanine is an essential amino acid in the human body. The phenylalanine ingested is partly used for protein synthesis, and the rest is converted into tyrosine by the action of phenylalanine hydroxylase, with only a small amount of phenylalanine being converted into phenylpyruvic acid through a minor metabolic pathway under the action of transaminase. Due to the reduced activity of phenylalanine hydroxylase, phenylalanine cannot be converted into tyrosine, resulting in an extremely high concentration of phenylalanine in the blood, cerebrospinal fluid, and tissues. Through a bypass metabolism, a large amount of phenylpyruvic acid, phenylacetic acid, phenyllactic acid, and p-hydroxyphenylacetic acid are produced. High concentrations of phenylalanine and its metabolites thus lead to brain damage. Due to the synthesis disorder of tyrosine, this also leads to symptoms such as light skin and hair pigmentation.