Dihydropyrimidine Dehydrogenase Deficiency
Disease Details
Family Health Simplified
- Description
- Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a genetic disorder characterized by the body's inability to properly break down thymine and uracil, leading to severe toxic reactions to certain chemotherapy drugs like 5-fluorouracil.
- Type
- Dihydropyrimidine dehydrogenase deficiency is a metabolic disorder. Its genetic transmission is autosomal recessive.
- Signs And Symptoms
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**Signs and symptoms of dihydropyrimidine dehydrogenase deficiency:**
1. **Neurological problems:**
- Intellectual disability
- Developmental delays
- Seizures
- Ataxia (loss of control of body movements)
2. **Physical abnormalities:**
- Microcephaly (small head size)
- Hypotonia (reduced muscle tone)
3. **Digestive issues:**
- Vomiting
- Feeding difficulties in infants
4. **Other symptoms:**
- Increased sensitivity to drugs, particularly fluoropyrimidines used in chemotherapy (e.g., 5-fluorouracil)
- Immunodeficiency signs (in some cases)
The severity of symptoms can vary, with some individuals showing mild symptoms or being asymptomatic, while others experience significant health challenges. - Prognosis
- The prognosis for individuals with dihydropyrimidine dehydrogenase (DPD) deficiency can vary widely. DPD deficiency can range from being asymptomatic to causing severe neurological problems. Individuals with partial deficiency may lead relatively normal lives with minor or no symptoms, while those with complete deficiency might experience developmental delays, seizures, and intellectual disability. It is important to diagnose the condition early, especially before administering certain chemotherapeutic drugs like 5-fluorouracil, as individuals with DPD deficiency can experience severe toxic reactions to these medications. Regular monitoring and supportive treatments can help manage symptoms and improve quality of life.
- Onset
- Dihydropyrimidine dehydrogenase deficiency typically presents in infancy or early childhood. Symptoms may include developmental delay, seizures, microcephaly, and other neurological abnormalities. However, the severity and exact onset of symptoms can vary widely among individuals.
- Prevalence
- Dihydropyrimidine dehydrogenase (DPD) deficiency is considered a rare metabolic disorder. The prevalence is estimated to be approximately 1 in 10,000 to 1 in 100,000 individuals.
- Epidemiology
- Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a rare metabolic disorder with an estimated incidence ranging from 1 in 10,000 to 1 in 100,000 individuals. This condition results from mutations in the DPYD gene, leading to diminished or absent activity of the enzyme dihydropyrimidine dehydrogenase. The deficiency can lead to severe toxic reactions to drugs like fluorouracil (5-FU), which are commonly used in chemotherapy. The exact prevalence may vary based on genetic background and geographical regions.
- Intractability
- Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) can present challenges in treatment, particularly when managing exposure to certain chemotherapeutic agents like 5-fluorouracil and capecitabine, as patients with this deficiency are at risk for severe toxicity. However, the condition itself is not inherently intractable. Management typically involves avoiding these medications and monitoring for symptoms associated with the enzyme deficiency. Supportive treatments and genetic counseling may also play significant roles in managing the condition.
- Disease Severity
- Dihydropyrimidine dehydrogenase deficiency can vary in disease severity. Some individuals may remain asymptomatic, while others can experience a range of symptoms, including developmental delay, seizures, and neurological issues. Additionally, patients with this deficiency are at an increased risk of severe toxic reactions to certain chemotherapeutic drugs like 5-fluorouracil and capecitabine.
- Healthcare Professionals
- Disease Ontology ID - DOID:14218
- Pathophysiology
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Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a genetic disorder that results from mutations in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase. This enzyme is crucial for the breakdown of uracil and thymine, two pyrimidine bases of DNA. The deficiency leads to an accumulation of these substances in the body.
In individuals with DPD deficiency, the faulty breakdown process can affect the metabolism of certain chemotherapy drugs, notably 5-fluorouracil (5-FU) and its prodrug capecitabine. This can result in severe, toxic reactions to these treatments. Symptoms in individuals without chemotherapy exposure can include developmental delays, intellectual disability, and a range of neurological problems. The severity of the disorder can vary widely among affected individuals. - Carrier Status
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Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a genetic disorder that affects the breakdown of certain compounds in the body, including the chemotherapy drug fluorouracil. Here’s what you need to know about carrier status:
Carrier Status: Carrying a single mutated copy of the DPYD gene (heterozygous) typically does not cause symptoms and may not result in the condition. However, carriers might have partial enzyme activity and could experience adverse reactions to drugs metabolized by dihydropyrimidine dehydrogenase. Individuals with two mutated copies (homozygous) usually manifest the deficiency and associated symptoms. Carrier screening and genetic testing can help determine if an individual is a carrier.
Nan: Not applicable in the context of this genetic condition. - Mechanism
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Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a metabolic disorder characterized by the body's reduced ability to break down uracil and thymine, pyrimidine bases of DNA and RNA. The condition is primarily inherited in an autosomal recessive manner.
### Mechanism:
The enzyme dihydropyrimidine dehydrogenase (DPD) is crucial in the catabolic pathway of pyrimidines. This enzyme catalyzes the reduction of uracil and thymine into dihydrouracil and dihydrothymine, respectively. When DPD is deficient or non-functional, it leads to an accumulation of uracil and thymine in the body.
### Molecular Mechanisms:
1. **Gene Mutations:** DPD deficiency is typically caused by mutations in the DPYD gene, which encodes the DPD enzyme. These mutations can lead to a partially functional or entirely non-functional enzyme.
2. **Loss of Enzyme Activity:** Mutations in the DPYD gene can result in missense or nonsense mutations, splice site alterations, or insertions and deletions, all contributing to the reduced activity or absence of the enzyme.
3. **Metabolic Imbalance:** Due to the lack of DPD activity, uracil and thymine are not adequately converted into their dihydro forms, resulting in their accumulation. This can disrupt normal cellular function and has toxic effects, particularly affecting the nervous system.
4. **Interaction with Anti-Cancer Drugs:** DPD deficiency is clinically significant because the enzyme also metabolizes 5-fluorouracil (5-FU), a chemotherapy drug. Individuals with DPD deficiency can suffer severe toxicity when treated with standard doses of 5-FU, due to the impaired degradation of the drug.
5. **Enzyme Kinetics:** Structural changes due to mutations can alter the enzyme’s substrate affinity, destabilize the protein, or affect its ability to reach the active form, thereby reducing its catalytic efficiency.
Understanding these molecular mechanisms is crucial for diagnosing DPD deficiency, managing its symptoms, and preventing adverse drug reactions, especially in cancer therapeutics. - Treatment
- For dihydropyrimidine dehydrogenase deficiency (DPD deficiency), treatment primarily involves the avoidance of certain chemotherapeutic agents that are metabolized by dihydropyrimidine dehydrogenase, such as fluoropyrimidines (e.g., 5-fluorouracil and capecitabine). Patients with DPD deficiency should be monitored closely by healthcare professionals and may require alternative cancer treatment regimens that do not involve these drugs. Genetic testing can help in identifying DPD deficiency, guiding appropriate treatment to avoid severe toxicities.
- Compassionate Use Treatment
-
Dihydropyrimidine dehydrogenase (DPD) deficiency is a metabolic disorder that affects the body's ability to break down certain drugs and pyrimidines. There are currently no specific treatments approved solely for this deficiency, but there are approaches to manage the condition, especially concerning the administration of fluoropyrimidine drugs like 5-fluorouracil (5-FU) and capecitabine. These drugs are metabolized by the DPD enzyme, and individuals with DPD deficiency are at increased risk of severe toxicity from these treatments.
1. **Compassionate Use Treatment:** There is no widely recognized compassionate use treatment specific to DPD deficiency, but managing the condition typically involves avoiding or adjusting the dosage of fluoropyrimidine drugs to prevent toxicity.
2. **Off-label or Experimental Treatments:**
- **Uridine Triacetate:** This may be used off-label to treat severe toxicity in patients who have inadvertently received 5-FU or capecitabine. It acts as an antidote by providing uridine, which competes with the toxic metabolites of pyrimidine drugs.
- **Genetic Testing:** While not a treatment, genetic testing for mutations in the DPYD gene (the gene encoding DPD) is recommended before initiating treatment with drugs like 5-FU or capecitabine. This can guide in adjusting dosages or choosing alternative therapies to avoid severe toxic side effects.
Management of DPD deficiency primarily focuses on avoiding or modifying the use of certain drugs that the enzyme metabolizes, with genetic testing playing a crucial role in personalized treatment planning. - Lifestyle Recommendations
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For individuals with dihydropyrimidine dehydrogenase (DPD) deficiency, lifestyle recommendations mainly focus on managing the condition and avoiding complications:
1. **Medication Management**: Since DPD deficiency affects the body's ability to break down certain chemotherapy drugs like 5-fluorouracil (5-FU) and capecitabine, it is crucial to inform healthcare providers about the condition to ensure appropriate medication choices and dosages.
2. **Regular Monitoring**: Regular medical check-ups with a healthcare provider are recommended to monitor for any potential health problems and to manage any existing conditions effectively.
3. **Balanced Diet**: Maintaining a balanced and nutritious diet can help support overall health and wellness. There is no specific diet required for DPD deficiency, but a well-rounded diet aids in general well-being.
4. **Hydration**: Staying well-hydrated is typically beneficial for overall health.
5. **Physical Activity**: Engaging in regular physical activity as tolerated and recommended by a healthcare provider can help maintain physical health.
6. **Avoiding Stress**: Stress management techniques, such as meditation or yoga, can be beneficial, as chronic stress may exacerbate health issues.
7. **Education and Awareness**: Individuals and families should educate themselves about the condition to better understand potential risks and how to manage them.
8. **Genetic Counseling**: If there is a family history of DPD deficiency, genetic counseling may be helpful to understand the inheritance pattern and implications for family members.
It is essential to work closely with healthcare providers to tailor these recommendations to individual needs and circumstances. - Medication
-
Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a metabolic disorder that affects the body's ability to break down certain medications, particularly the chemotherapy drug 5-fluorouracil (5-FU) and its prodrug capecitabine. Patients with DPD deficiency are at a higher risk of severe, potentially life-threatening side effects when treated with these drugs. Therefore, it's essential to test for DPD deficiency before initiating treatment with 5-FU or capecitabine to adjust the dosage or avoid these medications if necessary. Other chemotherapeutic agents that do not rely on dihydropyrimidine dehydrogenase for metabolism might be used as alternatives.
For other medications or specific recommendations on drug handling for those with DPD deficiency, consultation with a healthcare provider or specialist in genetic metabolic disorders is essential. - Repurposable Drugs
- There are currently no well-established repurposable drugs specifically for dihydropyrimidine dehydrogenase (DPD) deficiency. Management primarily focuses on avoiding or modifying the dosage of fluoropyrimidine drugs (such as 5-fluorouracil and capecitabine) used in chemotherapy, as DPD deficiency can result in severe toxicity when these drugs are administered. Genetic testing for DPD deficiency is recommended prior to initiating treatment with these agents to prevent adverse effects.
- Metabolites
- Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to the accumulation of certain metabolites. Specifically, there is an accumulation of uracil and thymine, which are normally broken down by the DPD enzyme. This accumulation can cause toxicity, particularly to 5-fluorouracil (5-FU) or capecitabine chemotherapy, as DPD is required to degrade these drugs. Elevated levels of these metabolites can be detected via blood or urine tests.
- Nutraceuticals
- For dihydropyrimidine dehydrogenase deficiency (DPD deficiency), there are no specific nutraceuticals that have been proven to treat the condition. Management primarily involves avoiding certain chemotherapy drugs, such as 5-fluorouracil (5-FU) and capecitabine, which require DPD for their metabolism. Nutraceuticals are not a standard part of treatment for this genetic deficiency. If you suspect you or someone you know has DPD deficiency, seek advice from a healthcare professional for proper diagnosis and management.
- Peptides
- Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is a metabolic disorder that affects the breakdown of pyrimidine bases (thymine and uracil). There is no direct involvement of peptides in the context of DPD deficiency; the core issue revolves around the impaired function of the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme deficiency can lead to severe toxicity when patients are treated with certain chemotherapeutic agents like 5-fluorouracil (5-FU) which are metabolized by DPD. Diagnosis often involves genetic testing and measurement of enzyme activity. Treatment for the condition primarily involves avoidance of specific medications that are broken down by the DPD enzyme.