Carnitine deficiency disorders in children.

摘要: Mitochondrial oxidation of long-chain fatty acids provides an important source energy for the heart as well skeletal muscle during prolonged aerobic work and hepatic ketogenesis long-term fasting. The carnitine shuttle is responsible transferring across barrier inner mitochondrial membrane to gain access enzymes beta-oxidation. consists three (carnitine palmitoyltransferase 1, acylcarnitine translocase, palmitoyl-transferase 2) a small, soluble molecule, carnitine, transport their esters. Carnitine provided in diet (animal protein) also synthesized at low rates from trimethyl-lysine residues generated protein catabolism. turnover (300-500 micromol/day) are <1% body stores; 98% stores intracellular (total levels 40-50 microM plasma vs. 2-3 mM tissue). removed by urinary excretion after reabsorption filtered load; renal threshold determines concentrations total stores. Because its key role acid oxidation, there has long been interest possibility that might be benefit genetic or acquired disorders production improve remove accumulated toxic acyl-CoA metabolites, restore balance between free acyl-CoA. Two have described children where supply becomes limiting oxidation: (1) A recessive defect muscle/kidney sodium-dependent, symporter, which presents infancy with cardiomyopathy hypoketotic hypoglycemia; treatment oral required survival. (2) Chronic administration pivalate-conjugated antibiotics pivaloyl-carnitine can lead depletion; tissue may become enough limit although no cases illness due deficiency described. There speculation supplements beneficial other settings (such defects--"secondary deficiency", chronic ischemia, hyperalimentation, nutritional deficiency), but efficacy not documented. formation abnormal acylcarnitines helpful expanded newborn screening programs using tandem mass-spectrometry blood spot profiles detect defects neonates. Carnitine-deficient diets (vegetarian) do much effect on pools adults. modest 50% reduction associated hyperalimentation infants, doubtful significance. above considerations indicate does rate-limiting unless extremely low; testing benefits require invasive endurance studies fasting cardiovascular work.