Dihydropyrimidine Dehydrogenase Deficiency

Abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency is an extremely rare autosomal recessive condition that was initially identified in the 1980s (Van Gennip et al. 1981). DPD is an enzyme that plays a role in the metabolism of pyrimidines, specifically the breakdown of thymine and uracil. Patients who lack this enzyme typically exhibit seizures and developmental delay in the first year of life before developing microcephaly with autistic characteristics, craniofacial dysmorphism, and growth restriction. Neonatal seizures are observed in a small percentage of patients sooner. Thymine and uracil excretion in the urine is elevated, which is the disease’s biochemical signature. Genetic testing or enzyme analysis can be used to confirm the diagnosis. Adult people who have this condition present with severe, potentially fatal toxicity after having chemotherapy with the pyrimidine analog 5-fluorouracil (5-FU) exist. While the adult form of this disease can affect heterozygous or homozygous people, the neonatal or infantile form is inherited as an autosomal recessive trait. Therefore, it is important to screen and counsel first-degree relatives of newborns who have been diagnosed with this disease about their potential for harmful reactions to 5-FU therapy (Balasubramaniam et al. 2014; Sharma et al. 2019).