Deranged isoleucine metabolism during ketotic attacks in patients with methylmalonic acidaemia

Abstract 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 acid, 3‐hydroxy‐ n ‐valeric acid, 3‐oxo‐ n ‐valeric acid, 2‐methyl‐3‐oxobutyric acid, citraconic acid and N ‐tiglylglycine. These compounds represent partly intermediary metabolites from the isoleucine degradation pathway and partly secondary metabolites of propionyl‐CoA and tiglyl‐CoA.