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| '''Other Names: '''
| | {{Infobox medical condition |
| PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica; Folling disease | | | name = Phenylketonuria |
| | | synonyms = PKU |
| | | image = |
| | | caption = |
| | | pronounce = |
| | | specialty = [[Genetics]], [[Pediatrics]] |
| | | symptoms = Intellectual disability, seizures, behavioral problems, mental disorders |
| | | complications = |
| | | onset = Early infancy |
| | | duration = Lifelong |
| | | types = |
| | | causes = Genetic ([[autosomal recessive inheritance]]) |
| | | risks = Family history |
| | | diagnosis = Newborn screening ([[blood test]]) |
| | | differential = |
| | | prevention = |
| | | treatment = Low-phenylalanine diet, [[Amino acid]] supplements |
| | | medication = Sapropterin |
| | | prognosis = Good with early treatment |
| | | frequency = 1 in 10,000 to 15,000 newborns in the United States |
| | | deaths = |
| | }} |
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| Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of [[phenylalanine]]. Phenylalanine is one of the building blocks ([[amino acids]]) of [[protein]]s. Humans cannot make phenyalanine, but it is a natural part of the foods we eat. However, people do not need all the phenyalanine they eat, so the body converts extra phenylalanine to another harmless amino acid, [[tyrosine]]. People with PKU cannot properly break down the extra phenylalanine to convert it to tyrosine. This means phenylalanine builds up in the person's blood, urine, and body. If PKU is not treated, phenylalanine can build up to harmful levels in the body. | | '''Phenylketonuria''' ('''PKU''') is a genetic disorder characterized by an inability in the body to metabolize the [[amino acid]] phenylalanine. Due to a deficiency in the enzyme phenylalanine hydroxylase, individuals with PKU accumulate high levels of phenylalanine in their blood, which can lead to various health problems including intellectual disability, seizures, and other serious medical issues. |
| [[File:Phenylalanine hydroxylase mutations 2.svg|thumb]]
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| | ==Causes== |
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| | PKU is caused by mutations in the PAH gene, which encodes the enzyme phenylalanine hydroxylase. This enzyme is crucial for the normal metabolism of phenylalanine, a building block of proteins. The mutations lead to reduced activity or complete absence of this enzyme, resulting in the accumulation of phenylalanine. PKU is inherited in an [[autosomal recessive]] pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected. |
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| == '''Types''' == | | ==Symptoms== |
| PKU varies from mild to severe. The most severe form is known as '''classic PKU'''. Without treatment, children with classic PKU develop permanent intellectual disability. Light skin and hair, seizures, developmental delays, behavioral problems, and psychiatric disorders are also common. Less severe forms, sometimes called "'''mild PKU'''", "variant PKU" and "non-PKU hyperphenylalaninemia", have a smaller risk of brain damage. Mothers who have PKU and no longer follow a phenylalanine-restricted diet have an increased risk of having children with an intellectual disability, because their children may be exposed to very high levels of phenylalanine before birth.
| | The primary symptoms of PKU include: |
| | * Intellectual disability |
| | * Seizures |
| | * Delayed development |
| | * Behavioral problems |
| | * Psychiatric disorders |
| | * Skin rashes (eczema) |
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| == '''Cause''' ==
| | If the disorder is not diagnosed early, and dietary management is not initiated, the buildup of phenylalanine can impair brain development leading to progressive intellectual disability and other neurological issues. |
| [[File:Inborn errors of metabolism of phenylalanine and tyrosine.svg|thumb]]
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| Mutations in the '''PAH gene''' cause phenylketonuria. The PAH gene provides instructions for making an enzyme called [[phenylalanine hydroxylase]]. This enzyme converts the amino acid [[phenylalanine]] to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed 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.
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| Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious health problems. Mutations 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.
| | ==Diagnosis== |
| | PKU is commonly diagnosed through newborn screening, which involves a simple [[blood test]] to measure phenylalanine levels. This test is typically performed within a few days of birth. Early diagnosis and treatment are crucial to prevent the symptoms and complications associated with PKU. |
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| Changes in other genes may influence the severity of PKU, but little is known about these additional genetic factors.
| | ==Treatment== |
| | The main treatment for PKU involves a diet low in phenylalanine, which necessitates strict dietary management to limit the intake of foods high in this amino acid, such as meat, fish, eggs, and dairy products. Special low-phenylalanine formulas and foods are used to support normal growth and development in children. |
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| == '''Inheritance''' ==
| | Additionally, some individuals may benefit from the drug sapropterin (a synthetic form of tetrahydrobiopterin or BH4), which can increase the tolerance to phenylalanine in some cases. Regular monitoring of phenylalanine levels in the blood is necessary to adjust dietary intake and ensure optimal management. |
| [[File:Autorecessive.svg|thumb|right|Autosomal recessive inheritance, a 25% chance]]
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| This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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| == '''Symptoms''' == | | ==Prognosis== |
| Phenylalanine plays a role in the body's production of melanin. The pigment is responsible for skin and hair color. Therefore, infants with the condition often have lighter skin, hair, and eyes than brothers or sisters without the disease.
| | With early and consistent treatment, individuals with PKU can lead healthy lives with normal intelligence. Ongoing research continues to explore new treatments and potential cures, including gene therapy. |
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| Other symptoms may include:
| | ==Epidemiology== |
| * Delayed mental and social skills
| | The incidence of PKU varies globally, but it is estimated to affect approximately 1 in 10,000 to 15,000 newborns in the United States. It is more common in certain populations, such as those of European descent. |
| * Head size much smaller than normal
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| * Hyperactivity
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| * Jerking movements of the arms or legs
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| * Mental disability
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| * [[Seizures]]
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| * Skin rashes
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| * [[Tremors]]
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| If PKU is untreated, or if foods containing [[phenylalanine]] are eaten, the breath, skin, ear wax, and urine may have a "mousy" or "musty" odor. This odor is due to a buildup of phenylalanine substances in the body.
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| == '''Diagnosis''' ==
| | [[Category:Genetic disorders]] |
| PKU can be easily detected with a simple blood test. All states in the United States require a PKU screening test for all newborns as part of the newborn screening panel. The test is generally done by taking a few drops of blood from the baby before the baby leaves the hospital.
| | [[Category:Metabolic disorders]] |
| | | [[Category:Inborn errors of metabolism]] |
| If the screening test is positive, further blood and urine tests are required to confirm the diagnosis. Genetic testing is also done.
| | {{medicine-stub}} |
| Screening for PKU is done with bacterial inhibition assay ([[Guthrie test]]), [[immunoassays]] using [[fluorometric]] or [[photometric]] detection, or amino acid measurement using [[tandem mass spectrometry]] (MS/MS). Measurements done using MS/MS determine the concentration of Phe and the ratio of Phe to tyrosine, the ratio will be elevated in PKU.
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| == '''Treatment''' ==
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| PKU is a treatable disease. Treatment involves a diet that is very low in [[phenylalanine]], particularly when the child is growing. The diet must be strictly followed. This requires close supervision by a registered dietitian or doctor, and cooperation of the parent and child. Those who continue the diet into adulthood have better physical and mental health than those who don't stay on it. "Diet for life" has become the standard most experts recommend. Women who have PKU need to follow the diet before conception and throughout pregnancy.
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| There are large amounts of phenylalanine in milk, eggs, and other common foods. The artificial sweetener NutraSweet ([[aspartame]]) also contains phenylalanine. Any products containing aspartame should be avoided.
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| There are several special formulas made for infants with PKU. These can be used as a protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids. Older children and adults use a different formula that provides protein in the amounts they need. People with PKU need to take formula every day for their entire life.
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| The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.
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| * '''[[Sapropterin]]''' (Brand name: Kuvan) approved to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Kuvan is to be used in conjunction with a Phe-restricted diet.
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| * '''[[Pegvaliase]] '''(Brand name: Palynziq) approved to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.
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| In 2018, the FDA approved an enzyme substitute called pegvaliase which metabolizes [[phenylalanine]].It is for adults who are poorly managed on other treatments.
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| '''[[Tetrahydrobiopterin]]''' (BH4) (a cofactor for the oxidation of phenylalanine) when taken by mouth can reduce blood levels of this amino acid in some people. Most people, however, with the "classical" sequence of mutations, will have little or no benefit.
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| == '''Prognosis''' ==
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| The outcome is expected to be very good if the diet is closely followed, starting shortly after the child's birth. If treatment is delayed or the condition remains untreated, brain damage will occur. School functioning may be mildly impaired.
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| If proteins containing phenylalanine are not avoided, PKU can lead to mental disability by the end of the first year of life.
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| == '''Epidemiology''' ==
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| The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.
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| {{Amino acid metabolic pathology}}
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| [[Category:Intellectual disability]] | |
| [[Category:Autosomal recessive disorders]]
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| [[Category:Amino acid metabolism disorders]] | |
| [[Category:Skin conditions resulting from errors in metabolism]] | |
| [[Category:Disorders causing seizures]]
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| [[Category:Biology of attention deficit hyperactivity disorder]]
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| [[Category:Rare diseases]]
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| [[Category:RTT]]
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| [[Category:Newborn screening]]
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| {{rarediseases}} | |
| {{stub}}
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| Phenylketonuria
|
|
|
| Synonyms
|
PKU
|
| Pronounce
|
|
| Specialty
|
Genetics, Pediatrics
|
| Symptoms
|
Intellectual disability, seizures, behavioral problems, mental disorders
|
| Complications
|
|
| Onset
|
Early infancy
|
| Duration
|
Lifelong
|
| Types
|
|
| Causes
|
Genetic (autosomal recessive inheritance)
|
| Risks
|
Family history
|
| Diagnosis
|
Newborn screening (blood test)
|
| Differential diagnosis
|
|
| Prevention
|
|
| Treatment
|
Low-phenylalanine diet, Amino acid supplements
|
| Medication
|
Sapropterin
|
| Prognosis
|
Good with early treatment
|
| Frequency
|
1 in 10,000 to 15,000 newborns in the United States
|
| Deaths
|
|
Phenylketonuria (PKU) is a genetic disorder characterized by an inability in the body to metabolize the amino acid phenylalanine. Due to a deficiency in the enzyme phenylalanine hydroxylase, individuals with PKU accumulate high levels of phenylalanine in their blood, which can lead to various health problems including intellectual disability, seizures, and other serious medical issues.
Causes
PKU is caused by mutations in the PAH gene, which encodes the enzyme phenylalanine hydroxylase. This enzyme is crucial for the normal metabolism of phenylalanine, a building block of proteins. The mutations lead to reduced activity or complete absence of this enzyme, resulting in the accumulation of phenylalanine. PKU is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.
Symptoms
The primary symptoms of PKU include:
- Intellectual disability
- Seizures
- Delayed development
- Behavioral problems
- Psychiatric disorders
- Skin rashes (eczema)
If the disorder is not diagnosed early, and dietary management is not initiated, the buildup of phenylalanine can impair brain development leading to progressive intellectual disability and other neurological issues.
Diagnosis
PKU is commonly diagnosed through newborn screening, which involves a simple blood test to measure phenylalanine levels. This test is typically performed within a few days of birth. Early diagnosis and treatment are crucial to prevent the symptoms and complications associated with PKU.
Treatment
The main treatment for PKU involves a diet low in phenylalanine, which necessitates strict dietary management to limit the intake of foods high in this amino acid, such as meat, fish, eggs, and dairy products. Special low-phenylalanine formulas and foods are used to support normal growth and development in children.
Additionally, some individuals may benefit from the drug sapropterin (a synthetic form of tetrahydrobiopterin or BH4), which can increase the tolerance to phenylalanine in some cases. Regular monitoring of phenylalanine levels in the blood is necessary to adjust dietary intake and ensure optimal management.
Prognosis
With early and consistent treatment, individuals with PKU can lead healthy lives with normal intelligence. Ongoing research continues to explore new treatments and potential cures, including gene therapy.
Epidemiology
The incidence of PKU varies globally, but it is estimated to affect approximately 1 in 10,000 to 15,000 newborns in the United States. It is more common in certain populations, such as those of European descent.
