title: Differentiation of long-chain fatty acid oxidation disorders using alternative precursors and acylcarnitine profiling in fibroblasts.
abstract: The differentiation of carnitine-acylcarnitine translocase deficiency (CACT) from carnitine palmitoyltransferase type II deficiency (CPT-II) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency from mitochondrial trifunctional protein deficiency (MTP) continues to be ambiguous using current acylcarnitine profiling techniques either from plasma or blood spots, or in the intact cell system (fibroblasts/amniocytes). Currently, enzyme assays are required to unequivocally differentiate CACT from CPT-II, and LCHAD from MTP. Over the years we have studied the responses of numerous FOD deficient cell lines to both even and odd numbered fatty acids of various chain lengths as well as branched-chain amino acids. In doing so, we discovered diagnostic elevations of unlabeled butyrylcarnitine detected only in CACT deficient cell lines when incubated with a shorter chain fatty acid, [7-2H3]heptanoate plus l-carnitine compared to the routinely used long-chain fatty acid, [16-2H3]palmitate. In monitoring the unlabeled C4/C5 acylcarnitine ratio, further differentiation from ETF/ETF-DH is also achieved. Similarly, incubating LCHAD and MTP deficient cell lines with the long-chain branched fatty acid, pristanic acid, and monitoring the C11/C9 acylcarnitine ratio has allowed differentiation between these disorders. These methods may be considered useful alternatives to specific enzyme assays for differentiation between these long-chain fatty acid oxidation disorders, as well as provide insight into new treatment strategies.
authors.affiliation: Kimberly H. Courtwright and Joseph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX, USA. dianero@baylorhealth.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Roe
authors.forename: B Z
authors.initials: BZ
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Vianey-Saban
authors.forename: E
authors.initials: E
authors.lastname: Struys
authors.forename: L
authors.initials: L
authors.lastname: Sweetman
authors.forename: C R
authors.initials: CR
authors.lastname: Roe
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D019748:Carbon-Carbon Double Bond Isomerases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D002478:Cells, Cultured; D004796:Clinical Enzyme Tests; D018076:DNA, Complementary; D003937:Diagnosis, Differential; D004746:Enoyl-CoA Hydratase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics; D010084:Oxidation-Reduction; D019998:Racemases and Epimerases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D005227:Fatty Acids; D009097:Multienzyme Complexes; C116917:acylcarnitine; C038784:fatty acid oxidation complex; C002844:pristanic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D000102:Acetyl-CoA C-Acyltransferase; D063991:Mitochondrial Trifunctional Protein; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases; D002331:Carnitine