MSUD is caused by pathogenic variants in the underlying genes BCKDHA (OMIM #608348), BCKDHB (OMIM #248611), or DBT (OMIM #248610), which abrogate the function of branched-chain ketoacid dehydrogenase (BCKDH), resulting in a partial or complete lack of branched-chain ketoacid dehydrogenase (BCKD) complex (EC 1.2.4.4) (Figure 2a). Here, BCKDHB is linked to maple syrup urine disease.