In humans, PDHA1 mutations constitute ∼80% of cases of Leigh disease displaying with severe early-onset neurodegenerative symptoms, PDC enzyme activity reduced to 30%, and lactic acidosis with ∼4-fold increase in pyruvate and lactate plasma levels (Foucher and Tubben, 2024; Gopal et al., 2023). Here, PDHA1 is linked to lactic acidosis.