This report describes two boys with a novel abnormality in long chain free fatty acid (LCFFA) disposition. Patient 1 presented at 1 year with non-ketotic hypoglycemia, hyper-ammonemia, and acute liver failure. Etiologic evaluation was unrevealing, and he eventually recovered. Multiple recurrences followed, requiring liver transplantation at age 5. Patient 2 presented at age 2 with hyperbilirubinemia and an AST of 3179 U/L. Progressive liver failure again required transplantation. Plasma FFAs in patient 1 were elevated during the final episode but normal between episodes; they were elevated during the sole episode in patient 2. Plasma and urine metabolic screens, and normal activities for many mitochondrial enzymes, assayed in cultured skin fibro-blasts, ruled out most disorders of mitochondrial fatty acid oxidation. Nevertheless, oxidation rates of selected LCFFAs in the cultured fibroblasts were reduced. Furthermore, in patient 1, hepatic tissue levels of representative LCFFAs were appreciably reduced while carnitine was increased, suggesting a defect in cellular LCFFA uptake. This was confirmed when the reduced rates of fibroblast fatty acid oxidation were significantly enhanced by prior permeabili-zation of plasma membranes, and by direct demonstration that uptake rates of representative LCFFAs were selectively reduced. The data indicate a defect in a specific transport process for LCFFA uptake. The process appears essential for maintaining hepatic ketogenesis and energy supply during fasting in infants and young children. COMMENTS
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