IMPAIRED FATTY-ACID OXIDATION IN CHILDREN ON VALPROIC ACID AND THE EFFECT OF L-CARNITINE

Fatty acid oxidation was studied in 12 patients (aged 3 to 19 years) r eceiving valproic acid (VPA), predominantly as monotherapy, before and after 1 month of L-carnitine supplementation (50 mg/kg/day po) in ord er to determine whether L-carnitine plays a role in preventing the hep atotoxic effects of this drug. Five of these patients were also studie d prior to VPA treatment. Only one patient taking VPA had an abnormall y low plasma free carnitine. Acyl-/free carnitine ratios were elevated in five patients on VPA and normalized after L-carnitine supplementat ion. Mean plasma concentrations of free fatty acids, beta-OH-butyrate, and cumulative excretion of (CO2)-C-13 after administration of 1-C-13 -octanoic acid were not changed by VPA or L-carnitine treatment. Urina ry dicarboxylic acids, acylglycines, and octanoylcarnitine were elevat ed during VPA therapy and unaltered by L-carnitine. These results sugg est that, in patients at low risk for VPA-induced hepatotoxicity (pati ents aged >2 years and taking VPA as monotherapy), VPA causes metaboli c abnormalities resembling those found in inborn errors of mitochondri al beta-oxidation which are not corrected by L-carnitine.