title: When do gut flora in the newborn produce 3-phenylpropionic acid? Implications for early diagnosis of medium-chain acyl-CoA dehydrogenase deficiency.
abstract: 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.
authors.affiliation: Division of Gastroenterology/Nutrition, Children's Hospital of Philadelphia, PA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bennett
authors.forename: A
authors.initials: A
authors.lastname: Bhala
authors.forename: S F
authors.initials: SF
authors.lastname: Poirier
authors.forename: M C
authors.initials: MC
authors.lastname: Ragni
authors.forename: S M
authors.initials: SM
authors.lastname: Willi
authors.forename: D E
authors.initials: DE
authors.lastname: Hale
mesh_terms: D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D004755:Enterobacteriaceae / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn / Q000382:microbiology*; D007422:Intestines / Q000254:growth & development / Q000382:microbiology*; D015997:Neonatal Screening; D010666:Phenylpropionates / Q000378:metabolism*
chemical_list: D010666:Phenylpropionates; C057466:3-phenylpropionylglycine; C024571:N-caproylglycine; C035253:3-phenylpropionic acid; D044944:Acyl-CoA Dehydrogenases; D005998:Glycine