title: Respiratory chain defects may present only with hypoglycemia.
abstract: Hypoglycemia occasionally results from oxidative phosphorylation deficiency, associated with liver failure. Conversely, in some cases of respiratory chain defect, the impairment in glucose metabolism occurs with normal hepatic function. The mechanism for this hypoglycemia remains poorly understood. We report here three unrelated children with hypoglycemia as the presenting symptom associated with oxidative phosphorylation deficiency but without liver dysfunction. Two patients had, respectively, complex III and complex IV deficiency and presented with long fast hypoglycemia. During a fasting test, the first patient showed evidence for impaired gluconeogenesis (progressive increase of plasma lactate and no decrease of alanine levels), whereas the second patient appeared to have impaired fatty acid oxidation (hypoketotic hypoglycemia with increased levels of non esterified fatty acids). The third patient presented with both long and short fast hypoglycemia related to complex IV deficiency. The mechanism of hypoglycemia for this patient may have been partly related to GH insufficiency, whereas impaired glycogen metabolism possibly accounted for short fast hypoglycemia. We suggest that hypoglycemia can be the presenting symptom for respiratory chain defects, through the possible reduction in cofactors resulting from oxidative phosphorylation deficiency, and that respiratory chain defects should therefore be considered in the differential diagnosis of hypoglycemia.
authors.affiliation: Service des Maladies Métaboliques, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, Paris 75015, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
authors.forename: Guy
authors.initials: G
authors.lastname: Touati
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabier
authors.forename: Michele
authors.initials: M
authors.lastname: Brivet
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Pascale
authors.initials: P
authors.lastname: DeLonlay
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D000596:Amino Acids / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007223:Infant; D008930:Mitochondria, Liver / Q000201:enzymology / Q000235:genetics*; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000235:genetics*; D010085:Oxidative Phosphorylation
chemical_list: D000596:Amino Acids; D044942:Acyl-CoA Dehydrogenase, Long-Chain