Miscellaneous Metabolic Disorders

Gene: DPYD

Green List (high evidence)

Well-established gene-disease association (see OMIM entry). Dihydropyrimidine dehydrogenase deficiency is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders) and is an inborn error of pyrimidine metabolism.
Sources: NHS GMS

Created: 4 Feb 2021, 12:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dihydropyrimidine dehydrogenase deficiency MIM#274270; 5-fluorouracil toxicity MIM#274270; Disorders of pyrimidine metabolism

Publications

• 8051923

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Some individuals with the enzyme deficiency are asymptomatic (OMIM).

5-FU is a common chemotherapy drug. Toxicity is based on haplotypes not single variants.
A list of genotype-phenotype predicted outcomes can be found here: (https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/)
A useful database: https://www.pharmgkb.org/gene/PA145/variantAnnotation

It is important to note that there are conflicting reports regarding patients' true response to 5-FU and their genotype + supposed predicted reaction

Dihydropyrimidine dehydrogenase deficiency - is a clinically heterogenous AR disorder showing wide variablity of clinical presentations, ranging from no symptoms to severe convulsive disorders w/ motor and mental retardation. (PMID 29152729)

Created: 17 Apr 2020, 4:39 a.m. | Last Modified: 17 Apr 2020, 4:39 a.m.

Panel Version: 0.2301

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
5-fluorouracil toxicity 274270; Dihydropyrimidine dehydrogenase deficiency 274270

Publications

• PMID: 29152729