Dihydropyrimidine Dehydrogenase Deficiency

Dihyropyrimidine dehydrogenase (DPYD) deficiency is an inherited disorder with large variability. It is due to the deficiency of the dihydropyrimidine dehydrogenase enzyme. Individuals may be severely affected or show no symptoms at all. Symptoms for those severely affected begin in infancy and include small head size, increased muscle tone, recurrent seizures and intellectual disability. Unfortunately, at this time, it cannot be determined who will show symptoms and who will not. Currently there is no cure for DPYD deficiency, but medical surveillance and care may help to improve some symptoms and overall condition of life. In addition, those who are severely affected, as well as those with no symptoms can develop severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5-FU), a commonly used medication for chemotherapy of many types of cancers. 5-FU has also been given topically for actinic keratoses and Bowen's disease. DPYD deficiency is caused by pathogenic variants in the DPYD gene.

DPYD is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

Carriers of the dihydropyrimidine dehydrogenase c.1905+1G>A pathogenic variant are at significantly increased risk to experience life-threatening myelosuppression upon 5-FU treatment, but otherwise typically show no signs or symptoms of the disorder. Routine testing for the exon 14-skipping pathogenic variant before 5-FU treatment is suggested by some physicians and testing of reproductive partners is recommended for carriers of DPYD deficiency.

DPYD deficiency is a rare disorder and it is not yet well determined how often it occurs in the general population.

Genetics Home Reference: DPYD (http://ghr.nlm.nih.gov/)

OMIM [DPYD: 274270] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing