- Also called:
- phenylpyruvic oligophrenia
- On the Web:
- National Center for Biotechnology Information - Phenylketonuria (PKU) (Oct. 28, 2026)
phenylketonuria
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What is phenylketonuria (PKU)?
Phenylketonuria (PKU) is an inherited metabolic disorder where the body can't process the amino acid phenylalanine. This is due to a lack of the enzyme phenylalanine hydroxylase, which normally converts phenylalanine into tyrosine.
The resulting buildup of phenylalanine can interfere with the central nervous system, leading to decreased production of neurotransmitters. If untreated, PKU can cause cognitive dysfunction, fair skin, and seizures. PKU is typically managed through a special diet that is low in phenylalanine, and infants can be screened for it soon after birth via a urine test.
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How do people get phenylketonuria?
People get phenylketonuria (PKU) through heredity. It is caused by an autosomal recessive gene, meaning that both parents must carry the gene for their child to have the condition. If both parents are carriers, there's a 25% chance their child will have PKU, a 50% chance the child will be a carrier, and a 25% chance the child will be completely unaffected. PKU results from the body's inability to metabolize phenylalanine because the enzyme phenylalanine hydroxylase is not active. This leads to high levels of phenylalanine in the body, which can cause neurological issues.
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What happens in the body when someone has PKU?
In phenylketonuria (PKU), the body can't properly break down phenylalanine, an amino acid. Normally, phenylalanine converts to tyrosine with the help of an enzyme called phenylalanine hydroxylase. In PKU, this enzyme is inactive, leading to high levels of phenylalanine in the blood, cerebrospinal fluid, and urine.
Excess phenylalanine and its byproducts disrupt processes in the central nervous system, reducing neurotransmitter production. This can cause nerve cell damage, evident within months of birth. Older individuals may experience nerve demyelination, leading to cognitive dysfunction, seizures, and abnormal brain activity. The retention of phenylalanine in tissues can also reduce melanin production, potentially causing fair skin, blond hair, and blue eyes.
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Why is it important to detect PKU early in life?
Early detection of phenylketonuria (PKU) is crucial because the resulting high levels of phenylalanine can interfere with metabolic processes in the central nervous system, leading to decreased production of neurotransmitters and subsequent nerve cell damage. If PKU is diagnosed early through newborn screening, intellectual disability can be avoided by maintaining a special diet low in phenylalanine throughout life. This dietary intervention prevents the toxic accumulation of phenylalanine and allows for normal intellectual and physical development.
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How is PKU managed or treated?
Phenylketonuria (PKU) management primarily involves a diet low in phenylalanine, achieved by avoiding high-protein foods like meat and dairy. Special phenylalanine-free amino acid drinks provide necessary nutrients, and glycomacropeptide (GMP) can replace amino acid drinks in solid foods. Pregnant women with PKU need to adhere to this diet to prevent harm to the unborn child.
While no drugs treat classical PKU, some individuals with hyperphenylalaninemia benefit from Kuvan, a synthetic form of tetrahydrobiopterin; however, they must still maintain a phenylalanine-restricted diet. Newborns in developed countries undergo genetic screening for early detection and intervention. Genetic counseling is also available.
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phenylketonuria (PKU), hereditary inability of the body to metabolize the amino acid phenylalanine. Phenylalanine is normally converted in the human body to tyrosine, another amino acid, by a specific organic catalyst, or enzyme, called phenylalanine hydroxylase. This enzyme is not active in individuals who have phenylketonuria. As a result of this metabolic block, abnormally high levels of phenylalanine accumulate in the blood, cerebrospinal fluid, and urine. Abnormal products of phenylalanine breakdown, such as highly reactive ketone compounds, can also be detected in the urine.
Excess phenylalanine and its abnormal metabolites interfere with various metabolic processes in the central nervous system that lead to decreased production of neurotransmitters (neuronal signaling molecules) such as dopamine. The first behavioral signs of nerve cell damage are usually evident in an affected child within four to six months of birth. Older individuals with phenylketonuria often have some degree of nerve demyelination (destruction of the myelin sheath that surrounds nerve fibres) that causes progressive symptoms of cognitive dysfunction, including mental retardation, epileptic seizures, and abnormal brain activity. The retention of phenylalanine in other tissues also leads to a decrease in the formation of melanin, a product of tyrosine metabolism that produces the pigment found in the skin, hair, and eyes. This may explain why persons with phenylketonuria generally have blond hair, blue eyes, and fair skin.
Phenylketonuria is transmitted by an autosomal recessive gene, which is present in about 1 in every 60 people. Statistically, two unaffected carriers of the gene can expect a 25 percent chance of having a child who is phenylketonuric, a 50 percent chance of having a child who is unaffected but is a carrier, and a 25 percent chance of having a completely normal child. Reliable tests are available to detect carriers of phenylketonuria, as well as infants who have the disorder. Approximately 1 in 12,000 to 15,000 newborn infants will show abnormally high plasma phenylalanine levels; out of these, about two-thirds will have the classic form of phenylketonuria.
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The remainder of individuals affected by phenylketonuria have deficiencies in tetrahydrobiopterin (or BH4), a chemical cofactor required for phenylalanine hydroxylase activity. Autosomal recessive defects in enzymes that synthesize tetrahydrobiopterin or that restore its catalytic activity can lead to a general disorder called hyperphenylalaninemia, characterized by abnormally high levels of phenylalanine in the blood and urine. The symptoms of hyperphenylalaninemia include impaired cognitive function, seizures, and behavioral and developmental abnormalities that may become apparent within months of birth.
The most effective treatment of phenylketonuria is maintenance of a diet low in phenylalanine. Such a diet is achieved by avoiding meat, dairy, and other foods high in protein. Intake of nutrients normally supplied by these foods is provided instead by special phenylalanine-free amino acid drinks. In addition, a protein called glycomacropeptide (GMP), which is formed during cheese making and thus can be isolated from whey, contains only trace amounts of phenylalanine and can be purified to be phenylalanine-free. GMP can be used in solid foods, and studies have shown that individuals with phenylketonuria are better able to adhere to their strict dietary regimens when given the option to consume GMP-fortified foods in place of amino acid drinks. These GMP foods also proved to be as safe and effective as traditional amino acid formulas. Pregnant women who have phenylketonuria must maintain a phenylalanine-restricted diet because the abnormally high levels of phenylalanine in their blood can severely damage an unborn child. While there are no drugs effective in treating classical phenylketonuria, a drug called Kuvan (sapropterin dihydrochloride), a synthetic form of tetrahydrobiopterin, is effective in treating some individuals with forms of hyperphenylalaninemia that are associated with deficiencies in tetrahydrobiopterin. Individuals taking Kuvan are instructed to remain on a phenylalanine-restricted diet.