PAH
phenylalanine hydroxylase
Normal Function
Health Conditions Related to Genetic Changes
Phenylketonuria
Hundreds of variants (also called mutations) in the PAH gene have been identified in people with phenylketonuria (PKU). This condition increase the levels of phenylalanine in the blood. If PKU is not treated, phenylalanine can build up to harmful levels, causing intellectual disability and other serious health problems.
Most of the variants that cause PKU change single amino acids in phenylalanine hydroxylase. For example, the most common variant in many populations replaces the amino acid arginine with the amino acid tryptophan at position 408 (written as Arg408Trp or R408W) in phenylalanine hydroxylase. Other PAH gene variants delete small amounts of DNA from the gene or disrupt the way the gene's instructions are used to make phenylalanine hydroxylase.
PAH gene variants reduce the activity of phenylalanine hydroxylase, preventing it from processing phenylalanine effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.
Classic PKU, the most severe form of the disorder, occurs in people who have very low levels of phenylalanine hydroxylase activity or who have no phenylalanine hydroxylase activity at all. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Variants in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.
More About This Health ConditionRelated Conditions
Phenylketonuria
Health Conditions Related to Genetic Changes
Hundreds of variants (also called mutations) in the PAH gene have been identified in people with phenylketonuria (PKU). This condition increase the levels of phenylalanine in the blood. If PKU is not treated, phenylalanine can build up to harmful levels, causing intellectual disability and other serious health problems.
Most of the variants that cause PKU change single amino acids in phenylalanine hydroxylase. For example, the most common variant in many populations replaces the amino acid arginine with the amino acid tryptophan at position 408 (written as Arg408Trp or R408W) in phenylalanine hydroxylase. Other PAH gene variants delete small amounts of DNA from the gene or disrupt the way the gene's instructions are used to make phenylalanine hydroxylase.
PAH gene variants reduce the activity of phenylalanine hydroxylase, preventing it from processing phenylalanine effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.
Classic PKU, the most severe form of the disorder, occurs in people who have very low levels of phenylalanine hydroxylase activity or who have no phenylalanine hydroxylase activity at all. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Variants in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.