MEDICAL ASPECTS OF KETONE-BODY METABOLISM

Ketone bodies are produced in the liver, mainly from the oxidation of fatty acids, and are exported to peripheral tissues for use as an ener gy source. They are particularly important for the brain, which has no other substantial non-glucose-derived energy source. The 2 main keton e bodies are 3-hydroxybutyrate (3HB) and acetoacetate (AcAc). Biochemi cally, abnormalities of ketone body metabolism can present in 3 fashio ns: ketosis, hypoketotic hypoglycemia, and abnormalities of the 3HB/Ac Ac ratio. Normally, the presence of ketosis implies 2 things: that lip id energy metabolism has been activated and that the entire pathway of lipid degradation is intact. In rare patients, ketosis reflects an in ability to utilize ketone bodies. Ketosis is normal during fasting, af ter prolonged exercise, and when a high-fat diet is consumed. During t he neonatal period, infancy and pregnancy, times at which Lipid energy metabolism is particularly active, ketosis develops readily. Patholog ic causes of ketosis include diabetes, ketotic hypoglycemia of childho od, corticosteroid or growth hormone deficiency, intoxication with alc ohol or salicylates, and several inborn errors of metabolism. The abse nce of ketosis in a patient with hypoglycemia is abnormal and suggests the diagnosis of either hyperinsulinism or an inborn error of fat ene rgy metabolism. An abnormal elevation of the 3HB/AcAc ratio usually im plies a non-oxidized state of the hepatocyte mitochondrial matrix resu lting from hypoxia-ischemia or other causes. We summarize the differen tial diagnosis of abnormalities of ketone body metabolism, as well as pertinent recent advances in research.