National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Phenylketonuria

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Other Names:
PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica; PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica; Folling disease See More
Categories:
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 proteins. 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.[1][2][3]

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.[1][2][3]

In most cases, PKU is caused by changes (pathogenic variants, also called mutations ) in the PAH gene. Inheritance is autosomal recessive manner.[1][2] Because PKU can be detected by a simple blood test and is treatable, PKU is part of newborn screening. Treatment for PKU normally involves a phenyalanine-restricted diet that is monitored carefully. Some children and adults with PKU may be helped by the medication sapropterin in combination with a low-phenylalanine diet.[1][2][3] Adults with high phenylalanine levels despite treatment may be helped by the medication pegvaliase.[3]
Last updated: 6/1/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 30 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] 		0003355
30%-79% of people have these symptoms
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation
[ more ] 		0010864
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology 0030680
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder
[ more ] 		0007018
Autosomal recessive inheritance 0000007
Blue irides
Blue eyes
0000635
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Depressivity
Depression
0000716
Dry skin 0000958
Eczema 0000964
Fair hair
Blond hair
Fair hair color
Flaxen hair color
Light colored hair
Sandy hair color
Straw colored hair
Towhead (hair color)
[ more ] 		0002286
Generalized hypopigmentation
Fair skin
Pale pigmentation
[ more ] 		0007513
Hyperphenylalaninemia 0004923
Hyperreflexia
Increased reflexes
0001347
Increased level of hippuric acid in urine 0410066
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Irritability
Irritable
0000737
Maternal hyperphenylalaninemia
High blood phenylalanine level in mother
0100610
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Obsessive-compulsive behavior
Obsessive compulsive behavior
0000722
Phenylpyruvic acidemia 0004920
Prenatal maternal abnormality 0002686
Psychosis 0000709
Reduced phenylalanine hydroxylase level 0005982
Scleroderma 0100324
Seizure 0001250
Self-mutilation
Deliberate self-harm
Self mutilation
[ more ] 		0000742
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • When an infant is newly diagnosed with PKU, the Children's PKU Network will send the parents an express pack of information to help the family get adjusted.  This packet is free of charge.  Click on the link to read more about how to obtain a packet.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Sapropterin (Brand name: Kuvan) - Manufactured by Biomarin Pharmaceutical Inc.
    FDA-approved indication: December 2014 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.
    National Library of Medicine Drug Information Portal
    Medline Plus Health Information
  • Pegvaliase (Brand name: Palynziq) - Manufactured by BioMarin Pharmaceutical
    FDA-approved indication: May 2018 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.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
PKU should be distinguished from BH4 deficiency.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Phenylketonuria. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • To help you stay up-to-date on ongoing PKU research visit the PKU News Web site.  Click on the link to view research information.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Phenylketonuria. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Phenylketonuria:
    NBS Connect
    PKU Patient Registry
    The PKU Registry
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • National Organization for Rare Disorders (NORD) has Disease-Specific Assistance Programs designed to help patients with out-of-pocket costs such as monthly insurance premiums or deductibles. In addition, some programs may provide financial assistance for additional expenses related to a patient's diagnosis such as travel to see a specialist.

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Parent and Caregiver Resources

  • In this NCATS Video Profile, Jennifer Payne discusses living with phenylketonuria (PKU). Left untreated, PKU results in psychological disorders, neurological deterioration, mental illness and brain damage. Dietary management and access to medical foods are a critical part of PKU care.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic. 
  • Genetics Home Reference (GHR) contains information on Phenylketonuria. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Phenylketonuria. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Regier DS, Greene CL. Phenylalanine Hydroxylase Deficiency. GeneReviews. January 5, 2017; http://www.ncbi.nlm.nih.gov/books/NBK1504/.
  2. Bodamer OA. Overview of phenylketonuria. June 21, 2016; https://www.uptodate.com/contents/overview-of-phenylketonuria.
  3. Rush ET. Phenylketonuria (PKU). Medscape Reference. May 31, 2018; https://emedicine.medscape.com/article/947781-overview.