In end-stage chronic liver failure, TD or ammonia exposure inhibits α-KGDH, thereby resulting in slowing TCA circulation, brain lactate accumulation, and loss of crucial brain protein activities due to oxidative damage of mitochondria (Schliess et al., 2002; Zhao et al., 2009; Pan et al., 2018). Here, OGDH is linked to thanatophoric dysplasia.