title: Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation.
abstract: Deficiency of carnitine/acylcarnitine translocase (CACT) is an autosomal recessive disorder of the carnitine cycle resulting in the inability to transfer fatty acids across the inner mitochondrial membrane. Only a limited number of affected patients have been reported and the effect of therapy on this condition is still not well defined. Here, we report a new patient with this disorder and follow the response to therapy. Our patient was the product of a consanguineous marriage. He presented shortly after birth with cardiac myopathy and arrhythmia coupled with severe non-ketotic hypoglycemia. Initial metabolic studies indicated severe non-ketotic C6-C10 dicarboxylic aciduria, plasma carnitine deficiency, and a characteristic elevation of plasma C:16:0, C18:1, and C18:2 acylcarnitine species. Enzyme assay confirmed deficiency of CACT activity. Molecular studies indicated that this child was homozygous, and both parents heterozygous, for a single bp change converting glutamine 238 to arginine (Q238R). Therapy with a formula providing most of the fat via medium chain triglycerides (MCT) and carnitine supplementation reduced the concentration of long-chain acylcarnitines and reversed cardiac symptoms and the hypoglycemia. These results suggest that carnitine and MCT may be effective in treating this defect of long-chain fatty acid oxidation.
authors.affiliation: Dipartimento Farmaco-Biologico, University of Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Iacobazzi
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
authors.forename: Rani
authors.initials: R
authors.lastname: Singh
authors.forename: Dietrich
authors.initials: D
authors.lastname: Matern
authors.forename: Piero
authors.initials: P
authors.lastname: Rinaldo
authors.forename: Cristina
authors.initials: C
authors.lastname: Amat di San Filippo
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
mesh_terms: D000108:Acetylcarnitine / Q000097:blood; D002331:Carnitine / Q000008:administration & dosage / Q000627:therapeutic use; D002333:Carnitine Acyltransferases / Q000172:deficiency* / Q000235:genetics*; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003998:Dicarboxylic Acids / Q000652:urine; D004035:Diet Therapy; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors; D008297:Male; D008954:Models, Biological; D020125:Mutation, Missense; D010375:Pedigree; D012016:Reference Values; D012529:Saudi Arabia / Q000208:ethnology; D016896:Treatment Outcome; D014280:Triglycerides / Q000008:administration & dosage
chemical_list: D003998:Dicarboxylic Acids; D014280:Triglycerides; D000108:Acetylcarnitine; D002333:Carnitine Acyltransferases; D002331:Carnitine