Phenylketonuria

Información en español Title

Other Names:

PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica; PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica; Folling disease See More

Categories:

Newborn Screening

Summary Summary

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

Symptoms Symptoms

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.

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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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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

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.

Treatment Treatment

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

Women with PKU who want to become pregnant can obtain a maternal express packet of information from the Children's PKU Network - free of charge - designed to assist women with their diet.
Wappner, et al. Management of Phenylketonuria for Optimal Outcome: A Review of Guidelines for Phenylketonuria Management and a Report of Surveys of Parents, Patients, and Clinic Directors. Pediatrics.1999;104:e68.
National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement: Phenylketonuria: Screening and Management October 16-18, 2000. Pediatrics. 2001;108:972-982.
You can find diet-related information on the PKU News Web site. Click on the link to view.

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.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

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 Research

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

Organizations Organizations

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

Children’s PKU Network
3306 Burmann Rd
Encinitas, CA 92024
Telephone: 858-756-0079
E-mail: pkunetwork@aol.com/
Website: http://www.pkunetwork.org/
National PKU Alliance
PO Box 501
Tomahawk, WI 54487
E-mail: http://www.npkua.org/About-NPKUA/Contact-Us
Website: http://www.npkua.org/
National PKU News
PO Box 43552
Montclair, NJ 07043
Telephone: 973-619-9160
E-mail: info@pkunews.org
Website: http://www.pkunews.org/

Do you know of an organization? We want to hear from you.

Living With Living With

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.

Learn More Learn More

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.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Phenylketonuria. This website is maintained by the National Library of Medicine.
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.

GARD Answers GARD Answers

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.

Have a question? Contact a GARD Information Specialist.