title: Glycine and L-carnitine therapy in 3-methylcrotonyl-CoA carboxylase deficiency.
abstract: 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). The 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 24 h of each of the following: L-carnitine 100 mg/kg per day and glycine 100, 175 and 250 mg/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.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000178:diet therapy / Q000188:drug therapy* / Q000652:urine; D019735:Carbon-Carbon Ligases; D002331:Carnitine / Q000627:therapeutic use*; D002648:Child; D002849:Chromatography, Gas; D018753:Diet, Protein-Restricted; D005260:Female; D005998:Glycine / Q000627:therapeutic use*; D006801:Humans; D008025:Ligases / Q000172:deficiency*; D009752:Nutritional Status
chemical_list: D008025:Ligases; D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase; D002331:Carnitine; D005998:Glycine