Abstract
LCD is a disorder of fatty acid β-oxidation with a wide range of clinical manifestations, including hypoglycemia without ketosls, hypotonia, cardiomegaly and C6-C14dicarboxylic aciduria. Patient R-1 presented with hypertrophic cardiomyopathy and hypotonia, while siblings H.C. and J.C. had recurrent episodes of hypoglycemia and dicarboxylic aciduria (Hale et. al. Ped. Res. 19:666, 1985; Naylor et. al. JIMD 2:19, 1980). R-1's fibroblasts oxidized [9,10(n)- 3H]palmitate at 28% of control levels, while H.C. and J.C. oxidized this substrate much more effectively (49 and 48% of control; p<0.01). However, LCADH activity in mitochondrial sonicates was ≤21% of control in all patients; the addition of 20 μM flavin adenine dinucleotide (FAD) increased LCADH activities to 27-36% of control in all three. Monospecific MCADH antisera lowered control LCADH activity 17%, demonstrating that human MCADH dehydrogenates palmityl-CoA. With MCADH antisera, LCADH activities in R-1 and J.C. fell to 11 and 6% of control, respectively. The observed heterognneity in clinical presentations and fibroblast oxidations were not explained by variations in LCADH activities or FAD responsiveness in these patients. H.C. and J.C. may have either a different mutation in LCADH than R-1, which preserves LCADH activity in vivo, or increased activity of peroxisomal β-oxidation.
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