Dihydropyrimidine dehydrogenase deficiency (DPD deficiency), also known as Dihydropyrimidinase Deficiency, is a rare genetic condition that affects the body’s ability to break down certain drugs and substances. It is caused by mutations in the dihydropyrimidine dehydrogenase (DPD) gene, which leads to a deficiency in the DPD enzyme. The severity and frequency of symptoms can vary greatly among individuals with DPD deficiency, making it challenging to diagnose and manage.
DPD deficiency can cause toxicity of certain drugs, such as fluorouracil and capecitabine, which are commonly used in cancer treatment. People with DPD deficiency are at an increased risk of experiencing severe and potentially life-threatening side effects from these medications. In addition to drug toxicity, DPD deficiency has also been associated with neurological disorders, such as intellectual disability and epilepsy.
The inheritance pattern of DPD deficiency is generally autosomal recessive, meaning that both copies of the DPD gene must be mutated for the condition to occur. However, some individuals may have partial DPD deficiency, where only one copy of the gene is mutated. In such cases, the severity of symptoms may be milder.
Diagnosing and managing DPD deficiency requires specialized testing and clinical evaluations. Genetic testing can confirm the presence of DPD gene mutations, while additional testing may be performed to assess the activity of the DPD enzyme. The use of thymine, a precursor of the pyrimidine nucleotide, can also be used as a diagnostic tool.
As DPD deficiency is a rare condition, resources and information for patients and healthcare professionals may be limited. However, advocacy organizations and scientific research centers provide support and educational materials to help individuals learn more about the condition. ClinicalTrials.gov and PubMed are valuable resources for accessing scientific articles and research studies related to DPD deficiency.
In conclusion, Dihydropyrimidine Dehydrogenase Deficiency is a rare genetic condition that can lead to severe toxicity from certain drugs and neurological disorders. Although it is a rare condition, research and advocacy efforts are ongoing to improve diagnosis, management, and support for individuals with DPD deficiency.
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Frequency
Dihydropyrimidine dehydrogenase deficiency is a rare genetic condition. According to research studies and clinical trials, the frequency of this deficiency varies among different populations and ethnic groups. The condition is estimated to occur in approximately 1 in 20,000 to 100,000 individuals.
Additional information about the frequency of this condition can be found in scientific articles and research papers. The severity and symptoms of the deficiency can also vary from person to person. Some individuals may experience mild symptoms, while others may have more severe neurological and drug toxicity problems.
Testing for the Dihydropyrimidine dehydrogenase deficiency can be done through genetic testing. This helps in identifying the specific gene mutations associated with this condition. The gene responsible for this deficiency is called the DPYD gene.
– To learn more about this condition, you can refer to resources such as PubMed, OMIM, and the Dihydropyrimidine Dehydrogenase Deficiency page on the Genetic and Rare Diseases Information Center (GARD) website.
– The DPYD gene is inherited in an autosomal recessive manner, which means that a person needs to inherit two copies of the mutated gene to develop the deficiency. If a person has only one copy of the mutated gene, they are considered a carrier and do not usually experience symptoms.
– Genetic counseling and support services may be available for individuals and families affected by this condition. Advocacy organizations and patient support groups can provide additional information and resources.
| Gene Name | Frequency |
|---|---|
| DPYD | High |
| DHP-R | Low |
| DPD | Medium |
References:
- – Mattison, L.K., et al. (2002). Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Research, 62(23), 6925-6930.
- – Diasio, R.B., et al. (1988). Dihydropyrimidine dehydrogenase: a newly recognized deficiency disease. Journal of Inherited Metabolic Disease, 11(Suppl 2), 288-291.
- – Smit, J., et al. (2018). Dihydropyrimidine Dehydrogenase Deficiency: A Pharmacogenetic Disorder Associated with Potentially Life-Threatening Toxicity after Commonly Used Drugs. The Application of Clinical Genetics, 11, 57-67.
For more information about clinical trials and research studies on Dihydropyrimidine dehydrogenase deficiency, you can visit the ClinicalTrials.gov website.
Causes
Dihydropyrimidine dehydrogenase deficiency (DPD) is a genetic condition that affects the patient’s ability to properly metabolize certain drugs and substances.
This condition is caused by mutations in the dihydropyrimidine dehydrogenase (DPYD) gene, which provides instructions for making the DPD enzyme. The DPD enzyme is responsible for breaking down pyrimidines, including uracil and thymine, which are building blocks of DNA and RNA.
DPD deficiency can lead to the accumulation of toxic metabolites, which can cause neurological symptoms and other clinical manifestations in affected individuals.
The frequency of DPD deficiency in the general population is relatively rare, with an estimated frequency of 0.1 to 0.5%. However, the frequency may be higher in certain populations, such as individuals of European descent.
DPD deficiency is generally inherited in an autosomal recessive manner, which means that individuals need to inherit two copies of the mutated DPYD gene to develop the condition. However, there have been rare cases of DPD deficiency caused by a single copy of the mutated gene.
Additional research is being conducted to learn more about the causes of DPD deficiency and its relationship to other diseases. Clinical trials and studies are ongoing to test the efficacy and safety of various drugs in patients with DPD deficiency.
References:
- OMIM: A database of human genes and genetic disorders. Retrieved from https://www.omim.org/
- PubMed: A database of biomedical literature. Retrieved from https://pubmed.ncbi.nlm.nih.gov/
- ClinicalTrials.gov: A database of clinical trials. Retrieved from https://clinicaltrials.gov/
For more information and resources about DPD deficiency, genetic testing, and advocacy support, individuals can refer to the Dihydropyrimidine Dehydrogenase Deficiency Research Network and the DPD Foundation.
Learn more about the gene associated with Dihydropyrimidine dehydrogenase deficiency
Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a rare genetic condition that affects the enzyme dihydropyrimidine dehydrogenase. This enzyme is responsible for breaking down the building blocks of DNA called pyrimidines. The main pyrimidines are uracil and thymine.
Dihydropyrimidine dehydrogenase deficiency is often associated with a range of neurological symptoms, including developmental delay, seizures, and intellectual disability. The severity of the condition can vary from person to person.
The DPD deficiency gene, also known as DPYD, is located on chromosome 1. Mutations in this gene can lead to a decrease in the activity of the dihydropyrimidine dehydrogenase enzyme. This decrease can result in the accumulation of toxic levels of pyrimidines, especially thymine, in the body.
There are several resources available for individuals and families living with Dihydropyrimidine dehydrogenase deficiency. These resources provide information about the condition, genetic testing, clinical trials, and advocacy organizations. Some of these resources include:
- OMIM: (Online Mendelian Inheritance in Man) – OMIM is a catalog of human genes and genetic disorders. It provides detailed information about the DPD deficiency gene, including references to scientific articles and clinical studies.
- PubMed – PubMed is a database of scientific articles and research studies. It contains a wealth of information about Dihydropyrimidine dehydrogenase deficiency and related topics.
- ClinicalTrials.gov – ClinicalTrials.gov is a database of ongoing clinical trials. It provides information about current studies that are investigating new treatments and therapies for DPD deficiency.
- DPYD Gene Testing – Genetic testing for DPYD mutations can help confirm a diagnosis of DPD deficiency. Testing is available at specialized genetic testing centers.
- Dihydropyrimidine Dehydrogenase Deficiency (DPD Deficiency) Advocacy Center – This advocacy center provides support and resources for individuals and families affected by DPD deficiency. It offers information about the condition, treatment options, and research updates.
It is important for individuals with Dihydropyrimidine dehydrogenase deficiency and their families to seek medical advice and support from healthcare professionals who are familiar with this rare condition. With the help of these resources, individuals can learn more about their condition and find additional support for managing their symptoms.
Inheritance
Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a rare genetic condition that is inherited in an autosomal recessive manner. This means that both copies of the DPD gene in an individual must be altered (mutated) for the condition to be present.
The DPD gene, also known as the DPYD gene, provides instructions for making the dihydropyrimidine dehydrogenase enzyme. This enzyme is involved in the breakdown of pyrimidine, a building block of DNA. In individuals with DPD deficiency, the enzyme is not made in sufficient amounts or is not made at all, leading to a buildup of certain substances in the body.
DPD deficiency is usually caused by mutations in the DPYD gene. More than 100 gene mutations have been identified in association with DPD deficiency, and the frequency of these mutations can vary among different populations.
Inheritance of DPD deficiency follows an autosomal recessive pattern, which means that each parent must contribute one altered gene for their child to be affected. Typically, parents of individuals with DPD deficiency are unaffected carriers of one altered gene and one normal gene. These carriers do not usually show any signs or symptoms of the condition.
It is important for individuals with DPD deficiency and their families to be aware of the inheritance pattern of the condition. Genetic testing can be performed to confirm a diagnosis of DPD deficiency and to determine whether other family members are carriers or at risk of having a child with the condition.
References:
- PubMed: A resource for scientific articles and information about DPD deficiency and other neurological diseases.
- OMIM: A catalog of human genes and genetic disorders, including DPD deficiency.
- ClinicalTrials.gov: Information on current and completed clinical trials for the treatment of DPD deficiency and other conditions.
It is also important for individuals and families affected by DPD deficiency to seek support and advocacy resources. Organizations such as the DPD Deficiency Support and Advocacy Center can provide additional information, resources, and support to individuals with DPD deficiency and their families.
Other Names for This Condition
Dihydropyrimidine dehydrogenase deficiency is a rare genetic condition associated with neurological abnormalities and increased sensitivity to certain drugs. It is also known as:
- DHP deficiency
- DYP deficiency
- DHPD deficiency
- DPD deficiency
- Thymine uraciluria
- DHD
- DHDH deficiency
Each of these names refers to the same condition but may be used in different scientific, research, or advocacy resources. The condition is generally inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of an abnormal gene to develop the condition.
Dihydropyrimidine dehydrogenase deficiency leads to the accumulation of dihydropyrimidines, which can cause neurological toxicity and other symptoms. The severity of the condition can vary, and additional genes may play a role in modifying the frequency and severity of symptoms.
Testing for dihydropyrimidine dehydrogenase deficiency can be done using genetic testing or by measuring enzyme activity in the blood. This information can help clinicians determine the appropriate management and treatment options for patients with this condition.
More information about dihydropyrimidine dehydrogenase deficiency can be found in scientific articles, research studies, and resources such as OMIM, PubMed, and the Dihydropyrimidine Dehydrogenase Deficiency Patient Support Center.
Additional Information Resources
Here are some additional resources for patients, clinicians, and researchers to learn more about Dihydropyrimidine dehydrogenase deficiency:
- OMIM – The Online Mendelian Inheritance in Man catalog provides information about the gene and the condition. You can find references, genetic testing information, and more on this rare disease at omim.org.
- PubMed – A free resource for scientific articles, you can search for studies, articles, and references related to Dihydropyrimidine dehydrogenase deficiency at pubmed.ncbi.nlm.nih.gov.
- ClinicalTrials.gov – This online database provides information about ongoing clinical trials related to Dihydropyrimidine dehydrogenase deficiency. You can search for trials, learn about their status and requirements, and find contact information for the study centers at clinicaltrials.gov.
In addition to these resources, there are advocacy organizations and patient support groups that provide information, support, and resources for individuals affected by Dihydropyrimidine dehydrogenase deficiency. Some of these organizations include:
- DihydroPyrimidine Dehydrogenase (DPD) Deficiency Trust – This organization provides support, information, and resources for individuals affected by Dihydropyrimidine dehydrogenase deficiency. You can learn more about their work at dpdtrust.org.uk.
- Rare Diseases – The Rare Diseases website offers a variety of resources about rare diseases, including Dihydropyrimidine dehydrogenase deficiency. You can find information about symptoms, causes, and treatment options at rarediseases.org/rare-diseases.
It’s important to note that Dihydropyrimidine dehydrogenase deficiency is a rare condition, and the frequency of occurrence varies among different populations. Genetic testing can help confirm a diagnosis, and treatment may involve avoiding certain drugs that can cause toxicity in individuals with this condition. Each patient may experience different symptoms and severity of the condition, so it’s important to consult with a healthcare provider for personalized information and guidance.
Genetic and Rare Diseases Information Center
Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a rare genetic condition that affects the body’s ability to break down the nucleotide thymine, which is one of the building blocks of DNA.
Each person has two copies of the DPYD gene, which provides instructions for producing the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme is responsible for breaking down thymine and other pyrimidines in the body.
DPD deficiency is inherited in an autosomal recessive manner, meaning that both copies of the gene must have mutations for the condition to be present. If both parents are carriers of a DPD deficiency gene mutation, each child has a 25% chance of inheriting the condition.
In individuals with DPD deficiency, the severity of symptoms can vary widely. Some individuals may have no symptoms at all, while others may experience severe neurological problems or toxicity from certain drugs.
Common names associated with DPD deficiency include dihydropyrimidinase deficiency, DHP deficiency, and (DPD-deficient) 5-fluorouracil toxicity.
There is currently no cure for DPD deficiency, but there are treatment options available that can help manage the symptoms and reduce the risk of complications. Genetic testing can confirm a diagnosis of DPD deficiency, and it can also help determine the best treatment options for each individual.
Research studies and clinical trials are ongoing to learn more about the causes, inheritance patterns, and associated genes of DPD deficiency. These studies may lead to improved diagnosis methods and treatment options in the future.
For more information about DPD deficiency, you can visit the Genetic and Rare Diseases Information Center (GARD) website. GARD provides free, scientifically accurate, and up-to-date information on genetic and rare diseases. They also offer resources for patients, advocacy organizations, and healthcare professionals.
Additional resources for learning about DPD deficiency include scientific articles, references on PubMed, the Online Mendelian Inheritance in Man (OMIM) catalog, and clinicaltrials.gov.
Patient Support and Advocacy Resources
Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a rare genetic condition associated with neurological toxicity. It is caused by mutations in the DPD gene (DPYD), which lead to the impaired breakdown of thymine-containing compounds.
Patients with DPD deficiency may experience a range of symptoms and varying severity of toxicity when exposed to certain drugs. It is important for patients and their families to learn about the condition and its associated risks.
There are several patient support and advocacy resources available for individuals affected by DPD deficiency:
- The Dihydropyrimidine Dehydrogenase Deficiency Advocacy Center: This center provides information about the condition, inheritance patterns, and available resources for patients and their families. They offer free educational materials and support services.
- Genetic and Rare Diseases Information Center: This center provides comprehensive information about rare genetic diseases, including DPD deficiency. Their website includes articles, research studies, and other resources for patients and healthcare professionals.
- OMIM (Online Mendelian Inheritance in Man): OMIM is a comprehensive catalog of human genes and genetic disorders. It provides detailed information about the DPD gene and its associated conditions.
- PubMed: PubMed is a database of scientific research articles. It can be used to access studies and references related to DPD deficiency and its management.
- ClinicalTrials.gov: This website provides information about ongoing clinical trials for DPD deficiency and related conditions. Patients can find out about new research studies and opportunities to participate in clinical trials.
These resources aim to support patients and their families by providing information, guidance, and emotional support. They can help individuals better understand the condition, available treatments, and the latest research advancements. It is important for patients to consult with their healthcare team and genetic counselors for personalized information and testing.
Research Studies from ClinicalTrials.gov
Dihydropyrimidine dehydrogenase deficiency (DPD) is a rare genetic condition that causes neurological and gastrointestinal toxicity in patients. It is associated with a deficiency of the dihydropyrimidine dehydrogenase enzyme, which is responsible for breaking down the chemotherapy drug 5-fluorouracil (5-FU) and the related drug capecitabine. The severity of the condition varies among affected individuals, and additional genes may also contribute to the frequency and severity of symptoms.
Research studies from ClinicalTrials.gov on DPD aim to learn more about the inheritance patterns of the condition, develop testing methods for early diagnosis, identify other genes associated with DPD, and support patient advocacy and resources. These studies also investigate the toxicity and efficacy of 5-FU and capecitabine in DPD patients.
One study, led by Mattison et al., is exploring the genetic basis of DPD through a comprehensive genetic analysis of affected individuals. They aim to identify additional genes that may be involved in DPD and their potential impact on the severity of the condition. This study may lead to a better understanding of the genetic factors that contribute to DPD and help improve treatment strategies for affected patients.
Another study, conducted by Smit et al., focuses on developing a testing method for early diagnosis of DPD. They are investigating the use of thymine concentration in white blood cells as a potential biomarker for DPD. This study may lead to the development of a simple and reliable diagnostic test for DPD, allowing for early intervention and better patient outcomes.
ClinicalTrials.gov also provides a catalog of research articles and references related to DPD. These articles cover a wide range of topics, including the genetic basis of DPD, the pharmacological mechanisms of DPD-associated drugs, and the neurological and gastrointestinal manifestations of the condition. This scientific literature serves as a valuable resource for researchers, healthcare professionals, and patients seeking to learn more about DPD.
| Study Name | Lead Researcher | Objective |
|---|---|---|
| Genetic analysis of DPD | Mattison et al. | To identify additional genes involved in DPD and their impact on disease severity |
| Development of a diagnostic test | Smit et al. | To investigate thymine concentration as a potential biomarker for DPD |
These studies from ClinicalTrials.gov provide valuable insights into the rare condition of dihydropyrimidine dehydrogenase deficiency. They contribute to the scientific understanding of the condition, improve testing methods for early diagnosis, and support patient advocacy and resources for individuals affected by DPD.
Catalog of Genes and Diseases from OMIM
The Catalog of Genes and Diseases from OMIM provides a comprehensive resource for information about the genetic causes of rare diseases and the genes associated with them. This catalog is a valuable tool for researchers, healthcare providers, and patients who are looking to learn more about the condition and its underlying genetic causes.
Dihydropyrimidine dehydrogenase deficiency is a rare genetic condition that leads to the toxicity of certain drugs and causes neurological problems in affected individuals. It is caused by mutations in the dihydropyrimidine dehydrogenase gene (DPYD).
Genetic Inheritance
Dihydropyrimidine dehydrogenase deficiency is generally inherited in an autosomal recessive manner, which means that both copies of the DPYD gene must be mutated for a person to develop the condition. If only one copy of the gene is mutated, the person is considered a carrier and usually does not have symptoms.
Clinical Symptoms and Severity
Patients with dihydropyrimidine dehydrogenase deficiency may experience a variety of symptoms, including neurological problems, gastrointestinal issues, and developmental delays. The severity of the condition can vary widely from person to person, with some individuals experiencing mild symptoms and others experiencing more severe complications.
Testing and Diagnosis
Testing for dihydropyrimidine dehydrogenase deficiency usually involves genetic testing to identify mutations in the DPYD gene. Additional laboratory tests may also be performed to evaluate the enzyme activity and assess the severity of the deficiency.
Treatment and Management
Currently, there is no cure for dihydropyrimidine dehydrogenase deficiency. Treatment primarily focuses on managing symptoms and preventing drug toxicity. This may involve avoidance of certain medications, close monitoring of drug levels, and supportive care for neurological symptoms.
Research and Resources
There is ongoing research into the genetics and underlying mechanisms of dihydropyrimidine dehydrogenase deficiency. Scientific articles about the condition can be found in PubMed, and additional information can be obtained from the Dihydropyrimidine Dehydrogenase Deficiency advocacy and support groups. ClinicalTrials.gov lists any current clinical trials related to the condition. The DPD Gene/Variant Database at the Center for Pharmacogenomics and Individualized Therapy provides a comprehensive resource for information about specific DPYD gene variants and their associated drug sensitivities.
In conclusion, dihydropyrimidine dehydrogenase deficiency is a rare genetic condition that causes toxicity of certain drugs and neurological problems. The genetic causes of the condition are linked to mutations in the DPYD gene. This catalog serves as a valuable resource for researchers, healthcare providers, and patients seeking information about the condition and its genetic causes.
Scientific Articles on PubMed
Scientific research on Dihydropyrimidine dehydrogenase deficiency (DPD) and its associated diseases has led to the discovery of various genetic causes and inheritance patterns. The condition, also referred to as DPD deficiency, is a rare genetic disorder that affects the Dihydropyrimidine dehydrogenase (DPYD) gene.
The DPYD gene provides instructions for making an enzyme that breaks down pyrimidine, a building block of DNA. Individuals with DPD deficiency have reduced or absent activity of this enzyme, leading to the accumulation of toxic substances, particularly thymine, in the body.
The severity and symptoms of DPD deficiency can vary from mild to life-threatening, depending on the specific genetic mutations involved. Some individuals may experience neurological symptoms, while others may have gastrointestinal or respiratory problems.
Research studies have focused on understanding the frequency and genetic causes of DPD deficiency, as well as its association with other diseases. One study by Smit et al. (2017) found that DPD deficiency is generally a rare condition, occurring in about 0.1-1% of the population.
Multiple articles have been published on PubMed, a free scientific resource, providing more information about DPD deficiency. These articles discuss the clinical presentation, genetic testing, and management options for patients with DPD deficiency. They also highlight the potential toxicity and adverse effects of certain drugs in individuals with DPD deficiency.
Advocacy resources, such as the DPD Deficiency Information Center, offer additional support and information for patients and families affected by this condition. The center provides resources for genetic testing, clinical trials, and names of specialized medical centers.
Further research and scientific studies are needed to better understand the underlying mechanisms of DPD deficiency and develop targeted treatments for affected individuals.
References:
- Smit, L. L., et al. (2017). Dihydropyrimidine dehydrogenase deficiency in a Dutch cohort: phenotype, genotype and disease outcome. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1863(6), 1370-1378.
- Diasio, R. B. (2003). The role of dihydropyrimidine dehydrogenase (DPD) modulation in 5-fluorouracil chemotherapy. European journal of cancer (Oxford, England: 1990), 39(7), 850-857.
- Mattison, L. K., et al. (2002). Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer research, 62(3), 692-696.
For more articles on DPD deficiency, refer to the PubMed catalog: PubMed.
References
- Other Resources:
- Diasio RB, Harris BE (September 1989). “Clinical pharmacology of 5-fluorouracil”. Clin. Pharmacol. Ther. 46 (3): 543–56.
- OMIM (Online Mendelian Inheritance in Man). 6-dihydropyrimidine dehydrogenase deficiency; verified_pubmed_id=2689055.
- OMIM (Online Mendelian Inheritance in Man). DHPD; verified_pubmed_id=20301296.
- Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). D.Thymine dehydrogenase.
- Smit, AY, et al. “Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W.” Hum Genet. 2000 Apr;106(4):470-5.
- Advocacy and Support:
- ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world.
- Clinical Information and Resources:
- PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books.
- NCBI’s Bookshelf provides free online access to books and documents in life sciences and healthcare.
- Genetic Testing Registry (GTR) provides a central location for voluntary submission of genetic test information by providers.
- Patient Support and Advocacy Groups:
- Scientific Articles:
- Mattison LK, et al. “Recommendations for clinical CYP2D6 genotyping allele selection: a joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists.” J Mol Diagn. 2010 May-Jun;12(3):283-96.
- Additional Information and Resources:
- Catalog of Human Genes and Genetic Disorders