Dihydropteridine reductase deficiency

Title

Other Names:

DHPR deficiency; Hyperphenylalaninemia, BH-4-deficient, C; Hyperphenylalaninemia due to dihydropteridine reductase deficiency; DHPR deficiency; Hyperphenylalaninemia, BH-4-deficient, C; Hyperphenylalaninemia due to dihydropteridine reductase deficiency; Phenylketonuria type 2; Quinoid dihydropteridine reductase deficiency; QDPR deficiency; PKU type 2 See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary Summary

Dihydropteridine reductase deficiency (DHPR) is a severe form of hyperphenylalaninemia (high levels of the amino acid phenylalanine in the blood) due to impaired renewal of a substance known as tetrahydrobiopterin (BH4).^[1] Tetrahydrobiopterin normally helps process several amino acids, including phenylalanine, and it is also involved in the production of neurotransmitters. If little or no tetrahydrobiopterin is available to help process phenylalanine, this amino acid can build up in the blood and other tissues and the levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid are also decreased.^[2] This results in neurological symptoms such as psychomotor delay, low muscle tone (hypotonia), seizures, abnormal movements, too much salivation, and swallowing difficulties. DHPR deficiency is caused by mutations in the QDPR gene. It is inherited in an autosomal recessive manner.^[1] Treatment should be started as soon as possible and includes BH4 supplementation usually combined with a diet without phenylalanine, folate supplementation, and specific medications to restore the levels of neurotransmitters in the brain.^[1]^[3]

Last updated: 12/28/2015

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
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Global developmental delay		0001263
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Cerebral calcification	Abnormal deposits of calcium in the brain	0002514
Choreoathetosis		0001266
Dystonia		0001332
Excessive salivation	Mouth watering Oversalivation Watery mouth [ more ]	0003781
Hyperphenylalaninemia		0004923
Hypertonia		0001276
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Irritability	Irritable	0000737
Muscular hypotonia	Low or weak muscle tone	0001252
Myoclonus		0001336
Progressive neurologic deterioration	Worsening neurological symptoms	0002344
Psychomotor retardation		0025356
Recurrent fever	Episodic fever Increased body temperature, episodic Intermittent fever [ more ]	0001954
Seizures	Seizure	0001250
Tremor	Tremors	0001337
Variable expressivity		0003828

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

Last updated: 10/1/2019

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.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

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.

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.
You can find diet-related information on the PKU News Web site. Click on the link to view.

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 Genetics Home Reference.

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
Differential diagnosis includes classical phenylketonuria, other causes of BH4 deficiencies (e.g. 6-Pyruvoyl-tetrahydropterin synthase deficiency, GTP cyclohydrolase I deficiency; see these terms), prenatal infections, Aicardi-Goutieres syndrome, infantile parkinsonism (e.g. dopamine transporter or tyrosine hydroxylase deficiency), and disorders affecting the white matter (e.g. neuronal ceroid lipofucsinosis, gangliosidosis, Alexander disease) (see these terms). Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnosis includes classical phenylketonuria, other causes of BH4 deficiencies (e.g. 6-Pyruvoyl-tetrahydropterin synthase deficiency, GTP cyclohydrolase I deficiency; see these terms), prenatal infections, Aicardi-Goutieres syndrome, infantile parkinsonism (e.g. dopamine transporter or tyrosine hydroxylase deficiency), and disorders affecting the white matter (e.g. neuronal ceroid lipofucsinosis, gangliosidosis, Alexander disease) (see these terms).

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

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.

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 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.

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.

In-Depth Information

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 Dihydropteridine reductase deficiency. 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.