Metabolic inflexibility and unusual catabolism in Leigh-like syndrome due to m.10191T>C

Abstract

Hypercatabolism is a well-known feature of mitochondrial diseases but some patients may present with hypometabolism, as the following case. Case report using standard investigation methods. The patient is a 32 years-old female with a Leigh-like syndrome due to the mtDNA variant m.10191T>C in MT-ND3. Leigh-like syndrome is characterized by symmetric basal ganglia or brainstem lesions plus involvement of organs other than the brain. The patient presented with hypometabolism, which did not respond to ketogenic diet but responded to fasting. The patient showed a Warburg-like effect, which resulted in reliance on glucose due to the exclusion of oxidative phosphorylation with an extremely low VO2max. The patient only entered substantial ketosis when all gluconeogenic substrates were removed. Prolonged survival in the index patient may have possibly resulted from this previously unreported protective mechanism to reduce oxidative stress. The unusual Warburg-like phenomenon was interpreted as a possible mechanism of patients with a mitochondrial disease to survive into adulthood. This case shows that mitochondrial disease can manifest with hypometabolism and that an unusual Warburg-like effect may be responsible in some patients with mitochondrial disease to survive into adulthood.