Dihydropyrimidine dehydrogenase deficiency
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.
Age of Onset
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
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.
X-linked 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.
Other Names (AKA)
DPD deficiency; Hereditary thymine-uraciluria; Familial pyrimidinemia
Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases
Dihydropyrimidine dehydrogenase (DPD) deficiency is a condition in which the body cannot break down the
DPD deficiency is caused by
All individuals with the DPD deficiency, regardless of the presence or severity of symptoms, are at risk for severe, toxic reactions to drugs called fluoropyrimidines which are used to treat
seizures intellectual disability
- growth retardation
- unusual physical features
- motor delay
- increased muscle tone
- hyperreflexia (exaggerated reflexes)
Some documented cases have also presented with other findings such as enlarged liver and spleen (
Everyone with DPD deficiency, regardless of whether or not they show any symptoms, is at risk to have a severe, toxic reaction to drugs known as fluoropyrimidines, the most common of which is 5-FU used to treat
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||
|5%-29% of people have these symptoms|
|Percent of people who have these symptoms is not available through HPO|
Degeneration of cerebrum
|Delayed speech and language development||
Deficiency of speech development
Delayed language development
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
[ more ]
|Failure to thrive||
[ more ]
Decreased muscle tone
Low muscle tone
[ more ]
[ more ]
More active than typical
Mental retardation, nonspecific
[ more ]
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ]
Abnormally small eyeball
Low or weak muscle tone
Involuntary, rapid, rhythmic eye movements
|Reduced dihydropyrimidine dehydrogenase level||0003654|
Paralysis of all four limbs
High urine uracil levels
Mutations in the DPYD gene result in reduced amounts of working DPD enzyme, interfering with the breakdown of uracil and thymine in cells. This results in excessive amounts of uracil and thymine in the blood, urine, and the fluid that surrounds the brain and spinal cord. It is currently poorly understood exactly how this cascade of events causes the signs and symptoms of the condition, or why only some infants with DPYD gene mutations have symptoms.
There is a breath test available that can measure DPD enzyme activity. In addition, there is evidence that genetic testing can identify many people with DPYD gene mutations. This may be important for
- 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.
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.
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.
- MedlinePlus Genetics contains information on Dihydropyrimidine dehydrogenase deficiency. This website is maintained by the National Library of Medicine.
- Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
- 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 Dihydropyrimidine dehydrogenase deficiency. Click on the link to view a sample search on this topic.
- Dihydropyrimidine dehydrogenase deficiency. Genetics Home Reference. Updated Sept 2015; https://ghr.nlm.nih.gov/condition/dihydropyrimidine-dehydrogenase-deficiency.
- Dihydropyrimidine dehydrogenase deficiency. Online Mendelian Inheritance in Man (OMIM). Updated 2012; https://www.omim.org/entry/274270.
- Fleger M Willomitzer J, Meinsma R, Alders M, Meijer J et al. Dihydropyrimidine dehydrogenase deficiency: Metabolic disease or biochemical phenotype?. JIMD Rep. Feb 2017; 37:49-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740048/.
- Ezzeldin H, Diasio R. Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. Clin Colorectal Cancer. September 2004; 4(3):181-189.
- Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M.. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. Dec 2013; 94(6):640-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831181/.
- Mir, Fazia. Fluorouracil Toxicity and DPYD. Medscape Reference. Updated Jan 5, 2016; https://emedicine.medscape.com/article/1746057-overview.