title: Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts.
abstract: Deficiency of the enzymes of mitochondrial fatty acid oxidation and related carnitine dependent steps have been shown to be one of the causes of the fasting-induced hypoketotic hypoglycemia. We describe here carnitine-acylcarnitine translocase deficiency in a neonate who died eight days after birth. The proband showed severe fasting-induced hypoketotic hypoglycemia, high plasma creatine kinase, heartbeat disorder, hypothermia, and hyperammonemia. The plasma-free carnitine on day three was only 3 microM, and 92% of the total carnitine (37 microM) was present as acylcarnitine. Treatments with intravenous glucose, carnitine, and medium-chain triglycerides had been tried without improvements. Measurements in fibroblasts confirmed deficient oxidation of palmitate and showed normal activities of the carnitine palmitoyltransferases I and II and of the three acyl-CoA dehydrogenases. A total deficiency of the carnitine-acyl-carnitine translocase was found in fibroblasts using the carnitine acetylation assay (1986. Biochem. J. 236:143-148). This assay has been further simplified by seeking conditions permitting application to permeabilized fibroblasts and lymphocytes.
authors.affiliation: Laboratory of Intermediary Metabolism, Clinical Research Institute of Montreal, Quebec, Canada.
authors.forename: S V
authors.initials: SV
authors.lastname: Pande
authors.forename: M
authors.initials: M
authors.lastname: Brivet
authors.forename: A
authors.initials: A
authors.lastname: Slama
authors.forename: F
authors.initials: F
authors.lastname: Demaugre
authors.forename: C
authors.initials: C
authors.lastname: Aufrant
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D002331:Carnitine / Q000097:blood; D002333:Carnitine Acyltransferases / Q000172:deficiency*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006327:Heart Block / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007003:Hypoglycemia / Q000201:enzymology* / Q000235:genetics; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D012016:Reference Values; D012867:Skin / Q000201:enzymology / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D007527:Isoenzymes; D044943:Fatty Acid Desaturases; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine