Abnormal urinary excretion of unsaturated dicarboxylic acids in patients with medium-chain acyl-CoA dehydrogenase deficiency

1990 
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most frequently described metabolic disorder of fatty acid oxidation in humans. Acute episodes are usually char- acterized biochemically by the appearance of nonketotic dicar- boxylic aciduria. In addition, other abnormal metabolites, such as sube-ylg1ycine, n-hexanoylglycine, 3-phenylpropionylglycine, and octanoylcamitine, are excreted in the urine. Urinary orga- nic acids were determined using dual capillary d." gas-li- quid chromatography and gas-liquid chromatography/mass spectrometry. In three cases of MCAD deficiency we observed a disproportionate increase in the excretion of unsaturated dicarboxylic acids compared to either fasting control children with expected ketotic dicarboxylic aciduria or patients with non- ketotic dicarboxylic aciduria not associated with MCAD defi- ciency. The most significant increase was in the urinary excretion of cu-4-decenedioic acid. Additionally, the urinary ex- cretions of czi-3-octenedioic and cir-5-decenedioic acids were slightly decreased whereas the excretion of cic-5-dodecenediojc acid was increased. m These data are consistent with the no- tion that as a result of MCAD deficiency the metabolic oxidation of unsaturated fatty acids such as linoleate and oleate is inhi- bited more than saturated fatty acids. -Tserng, K-Y., S-J. Jin, D. S. Kerr, and C. I,. Hoppel. Abnormal urinary excretion of unsaturated dicarboxylic acids in patients with medium-chain acyl-Cd dehydrogenase deficiency. J. Lipid Res. 1990. 31: 763-771. MATERIALS AND METHODS for MCAD deficiency, as other defects of fatty acid oxida- tion &O show increased urinary excretion of medium- chain dicarboxylic acids (3, e). Attempts to enhance the selectivity for the differential diagnosis based on urinary organic acid analysis have led to the identification of Uri- nary suberylglycine (5), hexanoylglycine (6), S-phenylpro- pionylglycine (7), octanoic acid (8), and octanoylcarnitine (8, 9) as possible specific marker compounds for MCAD deficiency (1). In three cases of MCAD deficiency, We have found ad- ditional unusual features of the dicarboxylic aciduria, which potentially may help differentiate this disorder from other defects of fatty acid oxidation. I~ MCAD defi- ciency, the urinary excretion of specific unsaturated medium-chain. (c 10-c 12) dicarboxylic acids is dispropor- tionately increased. This feature is simiIar to that observ- ed in rats treated with hypoglycin, an inhibitor of short-chain and medium-chain acyl-~oA dehydrogenases (10- 12). Urinary oqa& acid analysis
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