3-phenylpropionylglycine and hippuric-acid

Deficiency of medium-chain acyl-CoA dehydrogenase is a frequent and treatable metabolic defect, which can be diagnosed by detection of phenylpropionylglycine in urine after an oral load of phenylpropionic acid. We studied the determination of phenylpropionylglycine in urine by isocratic ion-exclusion chromatography on a cation-exchange column using water-sulphuric acid (pH values between 2 and 4) as mobile phase. Phenylpropionylglycine, phenylpropionic acid and hippuric acid exhibited high retention factors with only a slight decline at increasing solvent pH. This resulted in a good separation from interfering substances after direct injection of urine. We hypothesize that pi-pi interactions between the aromatic carbonic acids and the ion-exchange resin are responsible for the strong retention on the stationary phase. We conclude that, even in asymptomatic patients, determination of phenylpropionylglycine in urine after a phenylpropionic acid load by ion-exclusion chromatography is a rapid and reliable diagnostic tool for the detection of medium-chain acyl-CoA dehydrogenase deficiency.

Topics: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases; Chromatography, High Pressure Liquid; Glycine; Hippurates; Humans; Hydrogen-Ion Concentration; Phenylpropionates; Sensitivity and Specificity

The urinary excretion of metabolites of orally administered phenylpropionic acid (PPA) in 72 children, aged 2 days to 16 years, thought to be at-risk of medium acyl CoA dehydrogenase deficiency has been studied. Forty had presented as Reye Syndrome, 9 as a Reye-like syndrome and 24 were sibs of decreased RS, sibs of RLS cases or sibs of infants who had died suddenly and without explanation where an autopsy revealed the presence of very heavy fatty infiltration of the liver. These studies demonstrated that PPA metabolites are maximally excreted during the 3 hours following the oral load and that this urine collection should be diagnostic. PPA loading is a relatively simple, safe test which is part of the investigation of a patient suspected of having an inborn error of metabolism.

Topics: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases; Adolescent; Child; Child, Preschool; Glycine; Hippurates; Humans; Infant; Infant, Newborn; Phenylpropionates; Reye Syndrome; Risk Factors

Topics: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases; Chromatography, High Pressure Liquid; Glycine; Hippurates; Humans; Phenylpropionates; Time Factors