Abstract
A Japanese male neonate died at 13 d of age after presenting at 2 d of age with vomiting, dehydration, metabolic acidosis, liver dysfunction, and terminal rabdhomyolysis with myoglobinuria. Multiple urine organic acid analyses consistently revealed a markedly elevated excretion of lactic acid, 3-hydroxybutyric acid, and saturated and unsaturated C6-C16 dicarboxylic acids, with predominant C12-C16 species. Oxidation of [1-14C]octanoic acid in cultured skin fibroblasts was significantly reduced (0.59 nmol/h/mg of protein; controls, 1.93 ± 0.65), [1-14C]palmitic acid oxidation was 1.11 nmol/h/mg of protein (controls, 1.63 ± 0.41). A systematic study of the catalytic activities of nine enzymes of the β-oxidation cycle using the respective optimal substrate revealed a deficiency of a single enzyme not previously associated with a metabolic disorder, medium chain 3-ketoacyl-CoA thiolase (patient, 3.9 nmol/min/mg protein; controls (n = 6), 10.2 ± 2.3). Immunoprecipitation with antibodies raised against medium chain 3-ketoacyl-CoA thiolase revealed a 60% decrease compared with controls.
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Abbreviations
- GC/MS:
-
gas chromatography/mass spectrometry
- LCAD:
-
long chain acyl-CoA dehydrogenase
- MCAD:
-
medium chain acyl-CoA dehydrogenase
- MCKAT:
-
medium chain 3-ketoacyl-CoA thiolase
- SCAD:
-
short chain acyl-CoA dehydrogenase
- SCHAD:
-
short chain L-3-hydroxyacyl-CoA dehydrogenase
- TFP:
-
trifunctional protein
- VLCAD:
-
very long chain acyl-CoA dehydrogenase
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Acknowledgements
The authors thank M. Ohara for assistance with the manuscript, and Drs. Y. Koga and I. Nonaka for histologic analysis of skeletal muscle.
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Supported by the Mother and Child Health Foundation, and a grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education.
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Kamijo, T., Indo, Y., Souri, M. et al. Medium Chain 3-Ketoacyl-Coenzyme A Thiolase Deficiency: A New Disorder of Mitochondrial Fatty Acid β-Oxidation. Pediatr Res 42, 569–576 (1997). https://doi.org/10.1203/00006450-199711000-00002
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DOI: https://doi.org/10.1203/00006450-199711000-00002
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