Dihydropyrimidine Dehydrogenase (DPD) Deficiency As a Pediatric Disorder

Using induced pluripotent stem cell and mouse models, my lab is working to gain a better understanding of how DPD deficiency can contribute to intellectual disability.

Complete deficiency of dihydropyrimidine dehydrogenase because of aberrations in the DPYD gene can cause a rare childhood inborn error of metabolism.

Several case reports have suggested an association between severe DPD deficiency and a form of intellectual disability that is often accompanied by epileptic seizures, microcephaly, hypertonia, delayed motor skill development and autism spectrum disorder (ASD)-associated behaviors. Less severe, hemizygous chromosome deletions encompassing part of the DPYD gene have also been suggested to contribute to ASD independent of intellectual disability.

However, the mechanisms by which DPD deficiency contributes to intellectual disability and ASD are poorly understood.

Our goal is to provide information that can be used to develop effective means to prevent or reduce the severity of this metabolic condition.