Nucleotide metabolism disorders
Gene: DPYD
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 GMSCreated: 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
Variants in this GENE are reported as part of current diagnostic practice
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
gene: DPYD was added gene: DPYD was added to Nucleotide metabolism disorders. Sources: Expert Review Green Mode of inheritance for gene: DPYD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPYD were set to 8051923; 29152729 Phenotypes for gene: DPYD were set to Dihydropyrimidine dehydrogenase deficiency MONDO:0010130; Disorders of pyrimidine metabolism