DHODH and orotic aciduria: This metabolic pathway is essential for nucleotide homeostasis, cell growth, and proliferation.4 Defects in dihydroorotate dehydrogenase (DHODH) or UMP synthetase (UMPS), the enzymes catalyzing the next steps in the pathway after CAD, are associated with severe human disorders (Miller syndrome [OMIM 263750]5 and orotic aciduria [OMIM 258900]6).