Deranged isoleucine metabolism during ketotic attacks in patients with methylmalonic acidaemia

Two patients with methylmalonic acidaemia due to methylmalonyl-CoA mutase deficiency were studied for several years. Both exhibited at least two attacks of severe ketoacidosis, during which they excreted, in addition to methylmalonic acid, a number of abnormal compounds: 3-hydroxypropionic acid, 2-methyl-3-hydroxybutyric, 3-hydroxy-n-valeric acid, 3-oxo-n-valeric acid, 2-methyl-3-oxobutyric acid, citraconic acid and N-tiglyglycine. These compounds represent partly intermediary metabolites from the isoleucine degradation pathway and partly secondary metabolites of propionyl-CoA and tiglyl-CoA.