PRIMARY AND SECONDARY CARNITINE DEFICIENCY SYNDROMES

The objective of this article is to review primary and secondary cause s of carnitine deficiency, emphasizing recent advances in our knowledg e of fatty acid oxidation. It is now understood that the cellular meta bolism of fatty acids requires the cytosolic carnitine cycle and the m itochondrial beta-oxidation cycle. Carnitine is central to the translo cation of the long chain acyl-CoAs across the inner mitochondrial memb rane. The mitochondrial beta-oxidation cycle is composed of a newly de scribed membrane-bound system and the classic matrix compartment syste m. Very long chain acyl-CoA dehydrogenase and the trifunctional enzyme complex are embedded in the inner mitochondrial membrane, and metabol ize the long chain acyl-CoAs. The chain shortened acyl-CoAs are furthe r degraded by the well-known system in the mitochondrial matrix. Numer ous metabolic errors have been described in the two cycles of fatty ac id oxidation; all are transmitted as autosomal recessive traits. Prima ry or secondary carnitine deficiency is present in all these clinical conditions except carnitine palmitoyltransferase type I and the classi c adult form of camitine palmitoyltransferase type II deficiency. The sole example of primary camitine deficiency is the genetic defect invo lving the active transport across the plasmalemmal membrane. This cond ition responds dramatically to oral carnitine therapy. The secondary c arnitine deficiencies respond less obviously to carnitine replacement. These conditions are managed by high carbohydrate, low fat frequent f eedings, and vitamin/cofactor supplementation (eg, camitine, glycine, and riboflavin). Medium chain triglycerides may be useful in the dieta ry management of patients with inborn errors of the cytosolic carnitin e cycle or the mitochondrial membrane-bound long chain specific beta-o xidation system.