Phenylketonuria
Disease Details
Family Health Simplified
- Description
- Phenylketonuria (PKU) is a genetic disorder where the body cannot break down the amino acid phenylalanine, leading to its harmful buildup in the blood and brain.
- Type
- Phenylketonuria (PKU) is a metabolic disorder. It is inherited in an autosomal recessive pattern.
- Signs And Symptoms
- Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease is not detectable by physical examination at that time, because no damage has yet been done. Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by a heel prick, typically performed 2–7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding.If a child is not diagnosed during the routine newborn screening test and a phenylalanine-restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient levels of tyrosine) can interfere with infant development in ways that have permanent effects. The disease may present clinically with seizures, hypopigmentation (excessively fair hair and skin), and a "musty odor" to the baby's sweat and urine (due to phenylacetate, a carboxylic acid produced by the oxidation of phenylacetone). In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. Hyperactivity, EEG abnormalities, and seizures, and severe learning disabilities are major clinical problems later in life. A characteristic "musty or mousy" odor on the skin, as well as a predisposition for eczema, persist throughout life in the absence of treatment.The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible including asthma, eczema, anemia, weight gain, renal insufficiency, osteoporosis, gastritis, esophagus, and kidney deficiencies, kidney stones, and hypertension). Additionally, major depressive disorders occur 230% higher than controls; dizziness and giddiness occur 180% higher; chronic ischemic heart disease, asthma, diabetes, and gastroenteritis occur 170% higher; and stress and adjustment disorders occur 160% higher. In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all.
- Prognosis
-
Phenylketonuria (PKU) is a genetic disorder where the body cannot metabolize the amino acid phenylalanine. The prognosis largely depends on early diagnosis and strict adherence to a low-phenylalanine diet.
- **Prognosis:** If treated early and consistently, individuals with PKU can lead healthy lives with normal intellectual development. Without appropriate management, high levels of phenylalanine can lead to severe intellectual disability, neurological problems, and behavioral issues. Lifelong dietary management and regular monitoring are crucial.
- **Nan:** This seems incomplete. Did you mean to ask about a specific nanotechnology application in PKU treatment? Currently, the mainstay treatment is dietary management, but research is ongoing in various treatment avenues. - Onset
- The onset of phenylketonuria (PKU) typically occurs at birth. Newborn screening tests are routinely conducted to diagnose this condition early, allowing immediate dietary management to prevent long-term complications.
- Prevalence
- Phenylketonuria (PKU) is a rare genetic disorder. Its prevalence varies by population but is approximately 1 in 10,000 to 1 in 15,000 newborns in the United States and Europe.
- Epidemiology
- The average number of new cases of PKU varies in different human populations. United States Caucasians are affected at a rate of 1 in 10,000. Turkey has the highest documented rate in the world, with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than one case of PKU in 100,000 births. A 1987 study from Slovakia reports a Roma population with an extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding. It is the most common amino acid metabolic problem in the United Kingdom.
- Intractability
- Phenylketonuria (PKU) is not considered intractable if it is diagnosed early and managed properly. With early detection through newborn screening and strict adherence to a low-phenylalanine diet, individuals with PKU can lead healthy lives. However, if left untreated, PKU can result in severe intellectual disabilities, behavioral problems, and other neurological issues.
- Disease Severity
-
Phenylketonuria (PKU) is a genetic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase, which is necessary to metabolize the amino acid phenylalanine. Without proper management, phenylalanine can accumulate to harmful levels in the body.
### Disease Severity:
- **Mild to Severe**: The severity of PKU can vary. Classic PKU, the most severe form, can lead to intellectual disabilities, behavioral problems, and neurological issues if untreated. Mild forms, known as variant or non-classical PKU, may result in milder cognitive or developmental issues.
### Management:
- Early detection through newborn screening and dietary management (restricting phenylalanine intake) can prevent severe complications and lead to normal intellectual and developmental outcomes.
### Prognosis:
- With proper lifelong dietary management and regular monitoring, individuals with PKU can lead healthy lives with normal intelligence and development.
(EFFECTIVE MANAGEMENT IS CRUCIAL FOR PROGNOSIS) - Healthcare Professionals
- Disease Ontology ID - DOID:9281
- Pathophysiology
- When phenylalanine (Phe) cannot be metabolized by the body, a typical diet that would be healthy for people without PKU causes abnormally high levels of Phe to accumulate in the blood, which is toxic to the brain. If left untreated (and often even in treatment), complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder, as well as physical symptoms such as a "musty" odor, eczema, and unusually light skin and hair coloration.
- Carrier Status
-
Carrier status for Phenylketonuria (PKU):
Phenylketonuria is an autosomal recessive disorder, which means that it occurs when an individual inherits two copies of the mutated gene, one from each parent. Carriers of PKU have only one copy of the mutated gene and do not typically show symptoms of the disease. However, carriers can pass the mutated gene on to their offspring. If both parents are carriers, there is a 25% chance with each pregnancy that their child will have PKU, a 50% chance that their child will also be a carrier, and a 25% chance that their child will inherit neither copy of the mutated gene and be completely unaffected. - Mechanism
-
Phenylketonuria (PKU) is an inherited metabolic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH). This enzyme is responsible for converting the amino acid phenylalanine into tyrosine.
Mechanism:
- In PKU, mutations in the PAH gene lead to reduced or absent activity of the phenylalanine hydroxylase enzyme.
- This deficiency causes phenylalanine to accumulate in the blood and other tissues.
Molecular Mechanisms:
- The PAH gene is located on chromosome 12 (12q23.2), and various mutations in this gene can lead to PKU.
- These mutations hinder the enzyme's ability to bind its cofactor, tetrahydrobiopterin (BH4), or to stabilize its structure, leading to decreased enzyme function.
- Excess phenylalanine is toxic to the brain, leading to intellectual disabilities and other neurological issues if not managed through dietary restrictions.
Overall, PKU results from a genetic mutation affecting the normal catabolism of phenylalanine, requiring careful dietary management to prevent severe health outcomes. - Treatment
- PKU is not curable. However, if PKU is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication. If dietary treatment is not initiated within 2 weeks after birth, the child is likely to develop permanent intellectual disability, even if dietary interventions begin shortly thereafter.
- Compassionate Use Treatment
-
Phenylketonuria (PKU) is a metabolic disorder where the body cannot properly break down the amino acid phenylalanine. For compassionate use and off-label or experimental treatments, several approaches are being explored:
1. **Pegvaliase (Palynziq)**: This enzyme substitution therapy is approved for adults with PKU and may be used under compassionate use in certain cases not fully covered by standard protocols.
2. **Gene Therapy**: Experimental treatments are ongoing to correct the genetic mutation causing PKU. These are in the clinical trial phase and not yet widely available.
3. **Tetrahydrobiopterin (BH4) Supplementation**: Although primarily used in responsive forms of PKU, it can be considered off-label for non-responsive cases in certain circumstances.
4. **Large Neutral Amino Acids (LNAAs)**: These supplements help to inhibit phenylalanine transport across the blood-brain barrier. Their use can be considered experimental or off-label.
5. **Enzyme Substitution Therapy**: Research is ongoing into various enzyme replacement therapies that aim to break down phenylalanine in the bloodstream.
Patients considering these treatments should consult with specialists in metabolic disorders to weigh potential benefits and risks. - Lifestyle Recommendations
-
Lifestyle recommendations for phenylketonuria (PKU) include:
1. **Dietary Management**:
- Adhere to a lifelong low-phenylalanine (low-Phe) diet to avoid high levels of phenylalanine, which can cause brain damage. This involves avoiding high-protein foods such as meat, fish, eggs, dairy products, nuts, and soy.
- Use specially formulated low-protein products and medical foods designed for people with PKU.
- Regularly consume a special formula that provides essential amino acids and nutrients without phenylalanine.
2. **Regular Monitoring**:
- Routinely monitor blood phenylalanine levels to ensure they remain within a safe range. This can involve regular blood tests.
3. **Education and Support**:
- Seek guidance from healthcare professionals like dietitians who specialize in metabolic disorders.
- Participate in support groups for individuals and families affected by PKU.
4. **Medication**:
- In some cases, medication such as sapropterin dihydrochloride (Kuvan) may be prescribed to help lower blood phenylalanine levels in conjunction with the diet.
5. **Pregnancy Management**:
- Women with PKU should take extra care before and during pregnancy to maintain strict control of phenylalanine levels to prevent harm to the fetus.
6. **Avoiding Aspartame**:
- Avoid products containing the artificial sweetener aspartame, as it is converted to phenylalanine in the body.
Strict adherence to these lifestyle recommendations is crucial for managing PKU and preventing complications. - Medication
-
Phenylketonuria (PKU) is a genetic disorder where the body cannot properly break down the amino acid phenylalanine. Management primarily involves a strict diet low in phenylalanine to prevent its buildup, which can cause brain damage.
Medication options for PKU may include sapropterin dihydrochloride (Kuvan), which can help some individuals with PKU tolerate more dietary phenylalanine by increasing the activity of the enzyme phenylalanine hydroxylase. Another more recent medication is pegvaliase (Palynziq), an enzyme substitution therapy that helps break down phenylalanine. Both medications are particularly useful in conjunction with dietary management. - Repurposable Drugs
- Phenylketonuria (PKU) is a genetic disorder characterized by an inability to metabolize phenylalanine. There are currently no widely recognized repurposable drugs specifically for PKU. Treatment primarily involves a strict diet low in phenylalanine and, in some cases, supplementation with a medical food formula. Sapropterin dihydrochloride (Kuvan) is a drug specifically approved for some individuals with PKU, but it's not a repurposed drug; it's designed to enhance phenylalanine metabolism in those with residual enzyme activity. Research is ongoing into potential new therapies, but none are widely accepted as repurposable drugs for this condition as of now.
- Metabolites
- Phenylketonuria (PKU) is characterized by the accumulation of the amino acid phenylalanine and its metabolites, including phenylpyruvate, phenylacetate, and phenylactate, due to a deficiency in the enzyme phenylalanine hydroxylase.
- Nutraceuticals
-
Phenylketonuria (PKU) is a metabolic disorder where the body cannot break down the amino acid phenylalanine. To manage PKU, individuals usually follow a strict diet low in phenylalanine, which often includes medical foods or nutraceuticals designed to meet their nutritional needs while avoiding phenylalanine. Nutraceuticals may provide essential amino acids, vitamins, and minerals that PKU patients lack due to dietary restrictions. These products help ensure proper growth and development while minimizing the risk of phenylalanine accumulation and resultant neurological damage.
As of now, there are no specific nanotechnology-based treatments (nan) widely adopted for PKU, but research in nanomedicine may in the future offer innovative approaches for treatment or management. - Peptides
- Phenylketonuria (PKU) is a genetic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase, which leads to the accumulation of the amino acid phenylalanine in the body. The buildup of phenylalanine can cause a variety of health problems, including intellectual disability, seizures, and behavioral issues. Treatment involves a strict diet low in phenylalanine to prevent these complications.