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Dihydropyrimidine dehydrogenase deficiency

Other Names for this Disease
  • DPD deficiency
  • Familial pyrimidinemia
  • Hereditary thymine-uraciluria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I am interested in finding out information related to dihydropyrimidine dehydrogenase (DPD) in children - I am not interested in the form that presents after exposure to the cancer drug 5-fluorouracil. My son is about to turn 5 years old and was diagnosed with DPD at 4 months. Are there any specific articles that speak about infants and children that suffer from the deficiency?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is dihydropyrimidine dehydrogenase (DPD) deficiency?

Dihydropyrimidine dehydrogenase (DPD) deficiency is a condition in which the body cannot break down the nucleotides thymine and uracil. DPD deficiency can have a wide range of severity; some individuals may have various neurological problems, while others have no signs and symptoms. Signs and symptoms in severely affected individuals begin in infancy and may include seizures, intellectual disability, microcephaly, increased muscle tone (hypertonia), delayed motor skills, and autistic behavior.[1]  All individuals with the condition, regardless of the presence or severity of symptoms, are at risk for severe, toxic reactions to drugs called fluoropyrimidines which are used to treat cancer. Individuals with no symptoms may be diagnosed only by laboratory testing or after exposure to fluoropyrimidines. DPD deficiency is caused by mutations in the DPYD gene and is inherited in an autosomal recessive manner.[1]
Last updated: 8/20/2012

What are the clinical signs and symptoms in infants and children who have the inborn error of metabolism form of dihydropyrimidine dehydrogenase (DPD) deficiency?

All patients, including infants and children, with DPD deficiency exhibit the same clinical sign, complete or near complete absence of dihydropyrimidine dehydrogenase (DPD) enzyme activity. The symptoms of DPD deficiency, however, vary greatly from person to person, where some patients have not symptoms and others display any or all of the following[2][3]:

  • seizures
  • intellectual disability
  • growth retardation
  • unusual physical features
  • microcephaly
  • psychomotor retardation
  • increased muscle tone
  • autism
  • hyperreflexia (exaggerated reflexes)

Some documented cases have also presented with other findings such as enlarged liver and spleen (hepatosplenomegaly) and abnormal eye findings; however, these symptoms appear to be rarer.[2]


Last updated: 4/27/2010

What causes dihydropyrimidine dehydrogenase (DPD) deficiency?

DPD deficiency is caused by mutations in the DPYD gene. This gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase (DPD), which is involved in the breakdown of molecules called uracil and thymine. Uracil and thymine are building blocks of DNA, RNA, and molecules that serve as energy sources in cells.

Mutations in the DPYD gene result in deficiencies (to various degrees) of functional DPD, 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.[1]
Last updated: 8/20/2012

How is dihydropyrimidine dehydrogenase (DPD) deficiency diagnosed?

DPD deficiency may be diagnosed in various ways. In individuals with complete or profound DPD deficiency, laboratory testing can detect elevated levels of uracil and/or thymine in plasma or urine. Partial DPD deficiency is more difficult to detect, which has led to the development of a radioenzymatic test for the DPD enzyme. This test has remained the gold standard for diagnosing DPD deficiency even after the development of genetic testing for the condition, because of the complexity of the DPYD gene and the presence of multiple DNA sequence variations present in most affected individuals. Various types of cells and tissues can be examined this way.[4] More recently, a rapid, noninvasive, and cost-effective breath test was developed. This test permits the evaluation of DPD activity (normal activity and partial or profound deficiency) before the administration of fluoropyrmidine drugs such as 5-FU.[4]
Last updated: 8/20/2012

How might dihydropyrimidine dehydrogenase deficiency be treated in infants and children?

Currently, no treatment or cure exists for the inborn error of metabolism form of DHD deficiency. Symptoms usually remain the same throughout the person's life.[3]
Last updated: 4/27/2010

Are there any specific articles that speak about infants and children that suffer from dihydropyrimidine dehydrogenase (DHD) deficiency?

Yes. You can find relevant articles on the inborn error of metabolism form of DHD deficiency through PubMed, a searchable database of biomedical journal articles. Although not all of the articles are available for free online, most articles listed in PubMed have a summary available. To obtain the full article, contact a medical/university library or your local library for interlibrary loan. You can also order articles online through the publisher’s Web site. Using "dihydropyrimidine dehydrogenase deficiency inborn error" as your search term should help you locate some articles. Use the advanced search feature to narrow your search results. Click here to view a sample search. We recommend you visit PubMed regularly for updates.

The National Library of Medicine (NLM) Web site has a page for locating libraries in your area that can provide direct access to these journals (print or online). The Web page also describes how you can get these articles through interlibrary loan and Loansome Doc (an NLM document-ordering service). You can access this page at the following link You can also contact the NLM toll-free at 888-346-3656 to locate libraries in your area.
Last updated: 4/27/2010

  • Dihydropyrimidine dehydrogenase deficiency. Genetics Home Reference. November 2011; Accessed 11/28/2012.
  • Gibson KM, Jakobs C. Disorders of B- y-Amino Acids in Free and Peptide-Linked Forms. In: Scriver, Beaudet, Valle, Sly. The Metabolic & Molecular Bases on Inherited Disease. The McGraw-Hill Companies, Inc; 2001;
  • Kamatani N, Vincent MF, van den Berghe G. Purine and Pyrimidine Metabolism. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR. Emery and Rimoin's Principles and Practice of Medical Genetics. Philadelphia: Churchilll Livingstone; 2007;
  • 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.
Other Names for this Disease
  • DPD deficiency
  • Familial pyrimidinemia
  • Hereditary thymine-uraciluria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.