Disease Profile

Dihydropteridine reductase deficiency

Prevalence ?
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.

Unknown

Age of Onset

Infancy

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ICD-10

E70.1

Inheritance

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

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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

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X-linked 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.

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

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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.

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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.

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Not applicable

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Other Names (AKA)

DHPR deficiency; Hyperphenylalaninemia, BH-4-deficient, C; Hyperphenylalaninemia due to dihydropteridine reductase deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

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]

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.

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
Seizure
0001250
Tremor
0001337
Variable expressivity
0003828

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

      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

        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

          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.

            References

            1. Dihidropteridine reductase deficiency. Orphanet. September, 2014; https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=457. Accessed 12/28/2015.
            2. Tetrahydrobiopterin deficiency. Genetic Home Reference. July, 2011; https://ghr.nlm.nih.gov/condition/tetrahydrobiopterin-deficiency. Accessed 12/28/2015.
            3. Bodamer OA. Overview of phenylketonuria. June 21, 2016; https://www.uptodate.com/contents/overview-of-phenylketonuria.