Mitochondrial electron transport chain defect presenting as hypoglycemia,☆☆,

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Abstract

A profoundly deaf female infant was found to have hypoglycemia and lactic acidemia after an episode of decreased oral intake and vomiting. Electron transport chain (ETC) enzyme studies revealed a combination defect of complexes I, III, and IV in liver but not in skeletal muscle. This case highlights the fact that defects of the ETC are clinically highly heterogeneous and should be considered with hypoglycemia and lactic acidosis in the absence of a glycogen storage disorder. Moreover, ETC defects can occur with a biochemical profile suggestive of a fatty acid oxidation disorder. (J Pediatr 1997;130:431-6)

Section snippets

Clinical history

The proband, the second child of unrelated Australian parents, was born after an uneventful pregnancy by normal vaginal delivery at term. Her birth weight (3640 gm) and length (51 cm) were on the 50th percentile, but by the age of 6 months she was failing to thrive, with a fall in weight and length to the 3rd percentile. She had recurrent episodes of vomiting and was admitted to her local hospital at the age of 6 months with vomiting and drowsiness. No investigations were undertaken at this

METHODS

Urinary organic acid and acylglycine determinations and cultured skin fibroblast FAO studies were performed as previously reported. 7 Assay of the fibroblast whole cell 3-hydroxypalmitoyl-CoA (C16) dehydrogenase and 3-hydroxyacetoacetyl-CoA (C4) dehydrogenase was carried out by a method essentially similar to that of Wanders et al., 8 whereas assay of the mitochondrial ETC in skeletal muscle and liver homogenates and mitochondrial DNA point mutation analysis were performed as previously

Urinary organic acids and acylglycines

Urinary organic acid analysis during the initial period of hypoglycemia revealed a pattern of abnormalities suggestive of a fatty acid oxidation defect, possibly LCHAD deficiency (Table I) . However, another organic acid profile obtained after recovery from hypoglycemia did not show any abnormal compounds, with normalization of liver function tests.

Fasting study

The child had asymptomatic hypoglycemia (blood glucose concentration 1.6 mmol/L) after a relatively short fast of 12 hours performed at 18 months,

DISCUSSION

Mitochondrial DNA is a double-stranded, circular molecule that encodes subunits of four of the five respiratory chain complexes, two ribosomal chain complexes, and the 22 mitochondrion-specific translational RNAs. 13The majority of subunits of the ETC, however, are encoded by nuclear DNA, as are the many genes responsible for transcriptional regulation of mtDNA. Both mtDNA and nDNA defects may result in functional disturbance of the ETC. 14

Citrate synthase and complex II are entirely encoded by

Acknowledgements

We thank Dr. Sue Forrest, Murdoch Research Institute, Melbourne, for the MCAD mutation analysis, and Dr. Susan Arbuckle, New Children's Hospital, Westmead, for providing the liver histopathology photomicrograph.

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    From the Department of Clinical Genetics and the New South Wales Biochemical Genetics Service, Western Sydney Genetics Program, and the Department of Gastroenterology, Royal Alexandra Hospital for Children, Westmead, Australia; the Murdoch Research Institute and the State Neuropathology Service, University of Melbourne, Melbourne, Australia; and the Department of Paediatrics and Child Health, University of Sydney, Sydney, Australia.

    ☆☆

    Reprint requests: John Christodoulou, PhD, University Department of Paediatrics and Child Health, New Children's Hospital, PO Box 3515, Parramatta, New South Wales 2124, Australia.

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