Hereditary Thymine-Uraciluria / Dihydropyrimidine dehydrogenase deficiency (DPYD)
PrintDihydropyrimidine deyhyrogenase deficiency (DPD) or hereditary thymine-uraciluria (OMIM #274270) is an autosomal recessive disease characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. In children, DPD symptoms include convulsions, motor delay, and mental retardation, although a wide range of phenotypic variability has been reported. DPD also contributes to a severe reaction to the anticancer drug 5-fluorouracil (5-FU). This reaction includes stomatitis, leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, and neurologic symptoms, progressing to semicoma. DPYD mutations have been associated with Hereditary Thymine-Uraciluria/ Dihydropyrimidine deyhyrogenase deficiency.
Molecular testing for DPYD can be used to confirm diagnosis in individuals known or suspected to have hereditary thymine-uraciluria or dihydropyrimidine dehydrogenase. Also, carrier screening is available for at risk pregnancies as well as relatives for known familial mutation.
Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified by agarose gel electrophoresis. If full gene sequence analysis is requested, polymerase chain reaction (PCR) is used to selectively amplify regions of gDNA corresponding to the DPYD gene followed by double stranded sequencing in sense and antisense directions to detect sequence variations.
This Ambry test identifies >90% of described mutations (analytic sensitivity). Approximately 84% of patients with Dihydropyrimidine deyhyrogenase deficiency have a detectable mutation in the DPYD gene sequence (clinical sensitivity).
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into OrageneTM DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 4960 | DYPD Gene Sequence Analysis | 83891x1, 83894x24, 83898x23, 83904x46, 83909x46, 83912x1 |
| Technique | Days |
|---|---|
| DYPD Gene Sequence Analysis | 14-21 |
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