0A-S4-1

BRAIN ENERGY FAILURE SYNDROMES

De Vivo, DC

Columbia University, New York City, USA

Objective: To propose a classification of brain energy failure syndromes.

Methods: The lecturer has reviewed the neurochemical understanding of brain metabolism, the current hypothesis of glial-neuronal metabolic homeostasis, and the known human diseases that interfere with brain metabolism and function.

Results: Brain is dependent on glucose and ketone bodies as oxidizable fuel sources. Recent hypotheses suggest that glucose is metabolized to glycogen and to lactate in glia, and lactate is metabolized to carbon dioxide and water in the neuron. Glial ATP is generated by glycolysis and neuronal ATP is generated by oxidative phosphorylation. Glucose transporters (Gluts) facilitate the transport of glucose and monocarboxylic transporters (MCTs) facilitate transport of organic acids across tissue barriers including the blood-brain-barrier. The classification of brain energy failure syndromes utilizes these basic metabolic principles:

· Defects of fuel availability

- Hypoglycemic syndromes

- Hypoketonemic syndromes

· Defects of fuel transport

- Glut-1 deficiency syndrome

· Defects of fuel combustion

- Glycolytic diseases

- Mitochondrial diseases

Conclusion: The classification of brain energy failure syndromes facilitates the organization of diverse clinical disorders that cause neurological signs and symptoms, and allows one to craft treatments that may partially correct the energy failure and ameliorate the clinical condition. A primary example is the value of a ketogenic diet as treatment for the Glut-1 deficiency syndrome and pyruvate dehydrogenase deficiency. (Supported by Colleen Giblin Charitable Foundation)