Most of the patients with carnitine-palmitoyl-transferase deficiency (CPT) show reduced levels of blood ketone bodies in the postabsorptive state. In the present study, we have evaluated ketone body and glucose kinetics in patients with CPT deficiency. Intermediate metabolites of carbohydrate and lipid metabolism have also been studied. Ketone body (KB) turnover was measured by means of sequential intravenous bolus injections of 3-14C acetoacetate and 3-14C d(-) 3-hydroxybutyrate in four patients with liver, platelet, and muscle deficiency of CPT system and in eight normal overnight fasting subjects. 6-3H glucose was also injected, along with 3-14C ketone bodies to measure glucose turnover rate. Three out of four CPT deficiency patients had normal KB turnover, despite a marked reduction in liver CPT activity. Only one subject, with severe defect of CPT activity in liver, showed a significantly reduced, but still present rate of de novo synthesis of acetoacetate and 3-hydroxybutyrate (40 and 51 μmol/m-2/min-1 respectively) in comparison with control subjects (103 ± 14 and 157 ± 22 μmol/m-2/min-1). Blood concentrations of dicarboxylic adipic and suberic acids were significantly higher in CPT deficiency patients (0.035 ± 0.007 and 0.021 ± 0.005, mmol/L respectively) than in control subjects (0.008 ± 0.008 and 0.006 ± 0.003 respectively). Basal glucose turnover was increased in CPT deficiency patients (505 ± 13 μmol/m-2/min-1) in comparison with normal subjects (433 ± 18 μmol/m-2/min-1; P <.01) as well as clearance rates (127 ± 3 mL/m-2/min-1 and 91 ± 11 mL/m-2/min-1, respectively; P <.05). These findings suggest that ketone body synthesis does occur even if liver CPT activity is markedly impaired and that glucose utilization is higher in these subjects, where free fatty acid oxidation is impaired because of CPT deficiency.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism