3-phenylpropionylglycine and 3-phenylpropionic-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

Screening for medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency by urinary 3-phenylpropionylglycine may not be reliable in early infancy because young infants are not colonized with adult-type colonic flora. In this study we delineated the microbes that produce 3-phenylpropionic acid, the precursor of 3-phenylpropionylglycine. We found that the use of some antibiotics may alter gut flora, thereby confounding this method of screening for MCAD deficiency.

Topics: Acyl-CoA Dehydrogenase; Adult; Anti-Bacterial Agents; Bacteria, Anaerobic; Caproates; Child; Clostridium; Fatty Acid Desaturases; Glycine; Humans; Infant; Phenylalanine; Phenylpropionates

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

Urinary excretion of 3-phenylpropionylglycine (PPG) is a diagnostic marker for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. PPG is derived from 3-phenylpropionic acid (PPA), a product of anaerobic bacterial metabolism in the gut. To determine when the infant gut was colonized with PPA-producing bacteria, we cultured stool in prereduced thioglycollate broth from 93 apparently healthy infants. We analyzed the products of bacterial metabolism by gas chromatography/mass spectrometry for the presence of PPA. Trend analysis demonstrated a significant difference (P less than 0.001) in PPA production between early and later infancy. PPA was not detected in 84% of media isolated from stool collected from infants younger than four months. For older infants, 67% of the samples were PPA-positive. Thus, because the normal gut is not sufficiently colonized with PPA-producing bacteria before three to four months of age, PPG analysis alone is not a sensitive marker for the early detection of MCAD deficiency. Using stable isotope dilution mass spectrometry, we measured PPG and n-hexanoylglycine (HG) excretion in two well newborns with MCAD deficiency. HG, believed to be an endogenous metabolite associated with MCAD deficiency, was consistently above normal in all urine samples.

Topics: Acyl-CoA Dehydrogenases; Enterobacteriaceae; Feces; Female; Glycine; Humans; Infant; Infant, Newborn; Intestines; Neonatal Screening; Phenylpropionates

We report a family in whom a fatal case of medium-chain acyl-CoA dehydrogenase (MCAD; EC 1.3.99.3) deficiency was diagnosed by enzymatic analysis of heart tissue that had been stored for five years. Three healthy siblings underwent subsequent investigation with the 3-phenylpropionic acid loading test. All siblings had been asymptomatic; however, one (age 2.5 years) excreted large amounts of 3-phenylpropionylglycine in response to the load and exhibited an organic aciduria consistent with the diagnosis of MCAD deficiency. The other two siblings did not demonstrate 3-phenylpropionylglycinuria after the loading test. This case underlines the importance of considering family history and using appropriate diagnostic tests in the recognition of hereditary metabolic disorders.

Topics: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases; Family; Family Health; Female; Glycine; Humans; Infant; Lipid Metabolism, Inborn Errors; Myocardium; Phenylpropionates

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