Phenylketonuria
Phenylketonuria is an autosomal recessive inborn error of phenylalanine metabolism caused by variants in the gene encoding phenylalanine hydroxylase (PAH). PAH deficiency leads to accumulation of phenylalanine in the blood and brain. A dangerous buildup of phenylalanine can develop when a person with PKU eats protein-rich foods, such as milk, cheese, nuts or meat, and even grains such as bread and pasta. Untreated, PKU is characterized by irreversible intellectual disability, microcephaly, motor deficits, eczematous rash, autism, seizures, developmental problems, aberrant behaviour and psychiatric symptoms. Treatment aims to decrease blood phenylalanine concentrations. A low-phenylalanine diet starting early in childhood diminishes the chance of irreversible intellectual disabilities. In the 1960s, Guthrie developed a simple test to detect hyperphenylalaninemia to screen for PKU soon after birth.
