Metabolism of 1-¹³C-propionate in vivo in patients with disorders of propionate metabolism

Metabolism of propionate in human subjects was studied using bolus administration of l-¹³C-propionate i.v. or orally. The study population consisted of five patients with propionic acidemia (PA), eight with methylmalonic acidemia (MMA; four responsive to vitamin B₁₂), one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers. Concentrations of l-¹³C-propionate were measured in blood in three patients with PA, two with MMA, and two controls. Breath samples were obtained at intervals during 3 h after the dose, isotopic enrichment of¹³C0₂ was measured, and the cumulative percentage of recovery of¹³C was calculated from the individual’s predicted resting energy expenditure. Recovery of¹³C0₂ and half-time of l-¹³C-propionate in PA were significantly less than normal. The same parameters in MMA were below normal, but significantly greater than in PA. Recovery of¹³C0₂ was well correlated with clinical severity in PA, but did not correlate in MMA. Differences between MMA and PA may indicate different distribution of propionate pools, differences in inducibility of residual enzyme activities, or an alternate pathway for decarboxylation of propionate available in MMA but not PA. Only one patient with PA demonstrated increased¹³C0₂ production during biotin treatment. In a B₁₂-responsive MMA patient, no differences were noted within 2 d of initiating treatment with B₁₂, but there was an increase in¹³C0₂ production after 4 mo. Recovery of¹³C0₂ was normal in the patient with transcobalamin-II deficiency before and after treatment with vitamin B₁₂. In the patient with multiple carboxylase deficiency,¹³C0₂ generation was nearly normal while he was receiving his maintenance dose of biotin, and was not significantly changed after 3 and 7 d without biotin treatment, despite a decrease of 30% in lymphocyte propionyl-CoA carboxylase activity.