Learn About Dihydropyrimidine Dehydrogenase Deficiency

What is the definition of Dihydropyrimidine Dehydrogenase Deficiency?

Dihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity, with neurological problems in some individuals and no signs or symptoms in others.

In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. These affected individuals have neurological problems such as recurrent seizures (epilepsy), intellectual disability, a small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. Other affected individuals are asymptomatic, which means they do not have any signs or symptoms of the condition. Individuals with asymptomatic dihydropyrimidine dehydrogenase deficiency may be identified only by laboratory testing.

People with dihydropyrimidine dehydrogenase deficiency, including those who otherwise exhibit no symptoms, are vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency and build up to toxic levels in the body (fluoropyrimidine toxicity). Severe inflammation and ulceration of the lining of the gastrointestinal tract (mucositis) may occur, which can lead to signs and symptoms including mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Fluoropyrimidine toxicity may also lead to low numbers of white blood cells (neutropenia), which increases the risk of infections. It can also be associated with low numbers of platelets in the blood (thrombocytopenia), which impairs blood clotting and may lead to abnormal bleeding (hemorrhage). Redness, swelling, numbness, and peeling of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also occur.

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What are the causes of Dihydropyrimidine Dehydrogenase Deficiency?

Dihydropyrimidine dehydrogenase deficiency is caused by mutations in the DPYD gene. This gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase, which is involved in the breakdown of molecules called uracil and thymine. Uracil and thymine are pyrimidines, which are one type of nucleotide. Nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.

Mutations in the DPYD gene result in a lack (deficiency) of functional dihydropyrimidine dehydrogenase. Dihydropyrimidine dehydrogenase deficiency interferes with the breakdown of uracil and thymine, and results in excess quantities of these molecules in the blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). It is unclear how the excess uracil and thymine are related to the specific signs and symptoms of dihydropyrimidine dehydrogenase deficiency. Mutations that result in the absence (complete deficiency) of dihydropyrimidine dehydrogenase generally lead to more severe signs and symptoms than do mutations that lead to a partial deficiency of this enzyme.

Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of this enzyme leads to the drug buildup that causes fluoropyrimidine toxicity.

How prevalent is Dihydropyrimidine Dehydrogenase Deficiency?

Severe dihydropyrimidine dehydrogenase deficiency, with its early-onset neurological symptoms, is a rare disorder. Its prevalence is unknown. However, between 2 and 8 percent of the general population may be vulnerable to toxic reactions to fluoropyrimidine drugs caused by otherwise asymptomatic dihydropyrimidine dehydrogenase deficiency.

Is Dihydropyrimidine Dehydrogenase Deficiency an inherited disorder?

Dihydropyrimidine dehydrogenase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Depending on the severity of these mutations, people with two mutated copies of the DPYD gene in each cell may exhibit the signs and symptoms of this disorder, or they may be generally asymptomatic but at risk for toxic reactions to fluoropyrimidine drugs.

The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, people with one mutated copy of the DPYD gene in each cell may still experience toxic reactions to fluoropyrimidine drugs.

Who are the top Dihydropyrimidine Dehydrogenase Deficiency Local Doctors?
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Highly rated in
29
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Gynecologic Oncology
Obstetrics and Gynecology

Baptist Health - Conway

Conway, AR 

Alexander Burnett is a Gynecologic Oncologist and an Obstetrics and Gynecologist in Conway, Arkansas. Dr. Burnett has been practicing medicine for over 36 years and is rated as an Elite doctor by MediFind in the treatment of Dihydropyrimidine Dehydrogenase Deficiency. He is also highly rated in 29 other conditions, according to our data. His top areas of expertise are Dihydropyrimidine Dehydrogenase Deficiency, Endometrial Cancer, Endometrial Stromal Sarcoma, and Malignant Mixed Mullerian Tumor. He is board certified in Gynecological Oncology and licensed to treat patients in Arkansas. Dr. Burnett is currently accepting new patients.

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Highly rated in
3
conditions

Université Aix Marseille

Aix-en-provence, FR 

Joseph Ciccolini is in Aix-en-provence, France. Ciccolini is rated as an Elite expert by MediFind in the treatment of Dihydropyrimidine Dehydrogenase Deficiency. He is also highly rated in 3 other conditions, according to our data. His top areas of expertise are Dihydropyrimidine Dehydrogenase Deficiency, Low Potassium Level, Breast Cancer, and Non-Small Cell Lung Cancer.

 
 
 
 
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Elite
Highly rated in
1
conditions

Weston Park Hospital

Sheffield, ENG, GB 

Alice Dewdney is in Sheffield, United Kingdom. Dewdney is rated as an Elite expert by MediFind in the treatment of Dihydropyrimidine Dehydrogenase Deficiency. She is also highly rated in 1 other condition, according to our data. Her top areas of expertise are Dihydropyrimidine Dehydrogenase Deficiency, Renal Oncocytoma, Anal Cancer, and Nephrogenic Diabetes Insipidus.

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A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants.
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