title: In vivo stable isotope studies in three patients affected with mitochondrial fatty acid oxidation disorders: limited diagnostic use of 1-13C fatty acid breath test using bolus technique.
abstract: The in vivo oxidation of fatty acids (FA) of different chain length was investigated in three patients with documented mitochondrial FA oxidation disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were performed after oral administration of 1-13C butyric. 1-13C octanoic, and 1-13C palmitic acids. 13C/12C ratio in the expired oxidative end product CO2 was measured. The cumulative 13C elimination was calculated and expressed as a percentage of the administered dose. In the MADM patient the influence of carnitine therapy (or deprivation) on the utilization of 1-13C palmitic acid was also examined. In the MCAD and CPT I patients, the 1-13C butyric, 1-13C octanoic and 1-13C palmitic acids in vivo oxidation were similar to five healthy controls. In the MADM patient, the oxidation of 1-13C butyric and 1-13C octanoic acids were normal, whereas the metabolism of 1-13C palmitic acid ranged from 33% of 66% of controls. In this patient the serum carnitine level decreased from 60 to 27 mumol/l without carnitine supplementation. Clinically there was mild hypotonia. 1-13C palmitic acid oxidation compared to controls was 50%. After 2 further weeks of carnitine deprivation the serum carnitine was 10-15 mumol/l. Clinically he was very hypotonic and had a large liver. 1-13C Palmitic acid oxidation was 33%. After 6 weeks of readministration of carnitine (L-carnitine 100 mg/kg/day p.o.) the serum carnitine was 60 mumol/l and the patient was in good clinical condition. 1-13C palmitic acid oxidation was 66% compared to controls. Our study implies that this simple fatty acid breath test is not of diagnostic use for detection of enzymatic defects in FA oxidation disorders. The carnitine dependent 1-13C palmitic acid oxidation indicates that this test might be of some value in cases with primary or secondary carnitine deficiencies.
authors.affiliation: Department of Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: J
authors.initials: J
authors.lastname: Kneer
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Boulloche
authors.forename: M
authors.initials: M
authors.lastname: Brivet
authors.forename: B T
authors.initials: BT
authors.lastname: Poll-The
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D001944:Breath Tests; D002247:Carbon Isotopes; D002331:Carnitine / Q000627:therapeutic use; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction
chemical_list: D002247:Carbon Isotopes; D005227:Fatty Acids; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine