Glycine andl‐carnitine therapy in 3‐methylcrotonyl‐CoA carboxylase deficiency

Abstract

Summary: Genetic deficiency of 3‐methylcrotonyl‐CoA carboxylase (3‐MCC) is a rare inborn error of leucine metabolism producing an organic acidaemia. With accumulation of 3‐methylcrotonyl‐CoA, there is increased production of 3‐hydroxyisovaleric acid, the glycine conjugate (3‐methylcrotonylglycine), and the carnitine conjugate (3‐hydroxyisovalerylcarnitine). These conjugates represent endogenous detoxification products. We studied excretion rates of these conjugates at baseline and with glycine and carnitine therapy in an 8‐year‐old girl with 3‐MCC deficiency. Her preadmission diet was continued. Plasma and urine samples were obtained after 24h of each of the following:l‐carnitine 100mg/kg per day and glycine 100, 175 and 250mg/kg per day. Plasma and urinary carnitine levels were reduced by 80% and 50%, respectively with abnormal urinary excretion patterns. These normalized with carnitine therapy. Acylcarnitine excretion increased with carnitine therapy. The glycine conjugate, 3‐methylcrotonylglycine (3‐MCG), was the major metabolite excreted at all times and its excretion increased with glycine therapy. Clearly, in 3‐MCC deficiency the available glycine and carnitine pools are not sufficient to meet the potential for conjugation of accumulated metabolites, suggesting a possible therapeutic role for glycine and carnitine therapy in this disorder.