Dihydropyrimidine Dehydrogenase Deficiency
Dihydropyrimidine Dehydrogenase Deficiency
Pathogenesis (Nucleic Acid Disorder)
- Dihydropyrimidine dehydrogenase deficiency results in failure of uracil and thymine breakdown and toxic accumulation of these nucleotides.
Clinical
- Onset: Infancy
- Neurological manifestations: DIFFUSE. Cognitive Delay (w/Microcephaly), Motor Impairment (Hypertonia), Seizures, Vision Loss (Prevalent across variants), Neuropsychiatric (Autism phenotype).
- Notable Trigger: Toxic reaction to fluoropyrimidines (chemotherapeutic agents, eg 5-Fluorouracil and Capecitabine), due to inability to breakdown these chemotherapies – reaction includes pancytopenia (infection/bleeding), GI toxicity (nausea/vomiting), hand/foot rash and alopecia, and dyspnea.
Genetics
- DYPD gene mutation
- Autosomal recessive
References
- Calvo, Sherri; Collins, Heather; Greenberg, Kathleen, et. al at US National Library of Medicine, Genetics Home Reference. https://ghr.nlm.nih.gov