Rare Endocrinology News

Disease Profile


Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-5 / 10 000

US Estimated

Europe Estimated

Age of onset




E70.0 E70.1


Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

PKU; Phenylalanine hydroxylase deficiency; Oligophrenia phenylpyruvica;


Newborn Screening


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]


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.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

30%-79% of people have these symptoms
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggressive behaviour

[ more ]

Excessive, persistent worry and fear
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

Autosomal recessive inheritance
Blue irides
Blue eyes
Clouding of the lens of the eye
Cloudy lens

[ more ]

Cerebral calcification
Abnormal deposits of calcium in the brain
Dry skin
Fair hair
Blond hair
Fair hair color
Flaxen hair color
Light colored hair
Sandy hair color
Straw colored hair
Towhead (hair color)

[ more ]

Generalized hypopigmentation
Fair skin
Pale pigmentation

[ more ]

Increased reflexes
Increased level of hippuric acid in urine
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Maternal hyperphenylalaninemia
High blood phenylalanine level in mother
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

Obsessive-compulsive behavior
Obsessive compulsive behavior
Phenylpyruvic acidemia
Prenatal maternal abnormality
Reduced phenylalanine hydroxylase level
Deliberate self-harm
Self mutilation

[ more ]



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.


      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

        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.


            1. Regier DS, Greene CL. Phenylalanine Hydroxylase Deficiency. GeneReviews. January 5, 2017; https://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.