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.

Presentation and Diagnosis of Mitochondrial Disorders in Children

“…Growth failure presents as short stature in approximately 20% of mitochondrial patients [13], and endocrine problems include hypoparathyroidism, hypothyroidism, diabetes insipidus, diabetes mellitus, hypogonadism, and adrenocorticotropin hormone deficiency [12,17,21]. There are even several case reports of children with mitochondrial disorders with ketotic hypoglycemia as their only presenting sign [4,22]. Although such a presentation is uncommon, children may be dysmorphic, demonstrating features similar to those of fetal alcohol syndrome (microcephaly, round face, high forehead, featureless filtrum, low-set ears, and a short neck) [12].…”

Mechanisms behind decreased endogenous glucose production in malnourished children

“…Steatosis can lead to impairment of mitochondrial function (18) and ATP production (19). Decreased hepatic glucose production rates as found in inborn errors of metabolism in the oxidative phosphorylation pathway (20) or animal models of shock indicate a close link between mitochondrial dysfunction and impaired gluconeogenesis (21). Finally, signs of hepatic failure have been described in patients with severe malnutrition (22), which would also be associated with decreased EGP.…”

Pitfall in the Diagnosis of Fructose-1,6-Bisphosphatase Deficiency: Difficulty in Detecting Glycerol-3-Phosphate with Solvent Extraction in Urinary GC/MS Analysis

“…On the other hand, lactic acidosis with an elevated lactate/pyruvate ratio is a hallmark of mitochondrial respiratory chain disorders, which are more common than FBPase deficiency. Mochel et al (2005) reported that hypoglycemic patients with respiratory chain defects and mitochondrial respiratory chain disorders experience a variety of symptoms.…”