Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease

Abstract

The mitochondrial pyruvate oxidation route is a tightly regulated process, which is essential for aerobic cellular energy production. Disruption of this pathway may lead to severe neurometabolic disorders with onset in early childhood. A frequent finding in these patients is acute and chronic lactic acidemia, which is caused by increased conversion of pyruvate via the enzyme lactate dehydrogenase. Under stable clinical conditions, this process may remain well compensated and does not require specific therapy. However, especially in situations with altered energy demands, such as febrile infections or longer periods of fasting, children with mitochondrial disorders have a high risk of metabolic decompensation with exacerbation of hyperlactatemia and severe metabolic acidosis. Unfortunately, no controlled studies regarding therapy of this critical condition are available and clinical outcome is often unfavorable. Therefore, the aim of this review was to formulate expert-based suggestions for treatment of these patients, including dietary recommendations, buffering strategies and specific drug therapy. However, it is important to keep in mind that a specific therapy for the underlying metabolic cause in children with mitochondrial diseases is usually not available and symptomatic therapy especially of severe lactic acidosis has its ethical limitations.

Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth

“…Many of the metabolic disturbances seen in tko 25t larvae are consistent with previous studies of OXPHOS deficiency, although their exacerbation by high-sugar diet is novel. Elevated lactate, pyruvate and alanine are common findings in mitochondrial disease patients [ 23 ], considered to represent increased dependence on glycolysis under conditions where mitochondrial NADH re-oxidation is impaired [ 24 ]. tko 25t larvae showed decreased levels of the glycolytic intermediate immediately upstream of the rate-limiting step, i.e.…”

A 22-year-old woman with unexplained exertional dyspnoea

“…Even though the majority of mitochondrial disorders have no specific treatment,9 10 it has been reported that some forms may benefit from supplementation of carnitine, riboflavin and coenzyme Q10, as well as from programmes of physical training, leading to better exercise tolerance and to an improvement of symptoms 8 11–13. It has been in fact suggested that the use of these precursors of coenzymes may result in a clinical response by stimulation of enzyme activity 14.…”

Neonatal encephalocardiomyopathy caused by mutations in VARS2

“…Levocarnitine was supplemented due to low free carnitine levels. Additionally, the patient received riboflavin, thiamine, coenzyme Q 10 , and biotin in accordance with recently published recommendations [5]. The metabolic acidosis was accompanied by global respiratory insufficiency, which necessitated intubation and mechanical ventilation for four weeks.…”