Clinical Chemistry
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Clinical Chemistry 38: 278-281, 1992;
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Clinical Chemistry, Vol 38, 278-281, Copyright © 1992 by American Association for Clinical Chemistry

When do gut flora in the newborn produce 3-phenylpropionic acid? Implications for early diagnosis of medium-chain acyl-CoA dehydrogenase deficiency

MJ Bennett, A Bhala, SF Poirier, MC Ragni, SM Willi and DE Hale
Division of Gastroenterology/Nutrition, Children's Hospital of Philadelphia, PA.

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.


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Copyright © 1992 by the American Association for Clinical Chemistry.