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Relative efficiencies of plasma catechol levels and ratios for neonatal diagnosis of menkes disease.

AbstractBACKGROUND:
Menkes disease is an X-linked recessive neurodevelopmental disorder resulting from mutation in a copper-transporting ATPase gene. Menkes disease can be detected by relatively high concentrations of dopamine (DA) and its metabolites compared to norepinephrine (NE) and its metabolites, presumably because dopamine-beta-hydroxylase (DBH) requires copper as a co-factor. The relative diagnostic efficiencies of levels of catechol analytes, alone or in combination, in neonates at genetic risk of Menkes disease have been unknown.
METHODS:
Plasma from 44 at-risk neonates less than 30 days old were assayed for DA, NE, and other catechols. Of the 44, 19 were diagnosed subsequently with Menkes disease, and 25 were unaffected.
RESULTS:
Compared to unaffected at-risk infants, those with Menkes disease had high plasma DA (P < 10(-6)) and low NE (P < 10(-6)) levels. Considered alone, neither DA nor NE levels had perfect sensitivity, whereas the ratio of DA:NE was higher in all affected than in all unaffected subjects (P = 2 x 10(-8)). Analogously, levels of the DA metabolite, dihydroxyphenylacetic acid (DOPAC), and the NE metabolite, dihydroxyphenylglycol (DHPG), were imperfectly sensitive, whereas the DOPAC:DHPG ratio was higher in all affected than in all unaffected subjects (P = 2 x 10(-4)). Plasma dihydroxyphenylalanine (DOPA) and the ratio of epinephrine (EPI):NE levels were higher in affected than in unaffected neonates (P = 0.0015; P = 0.013).
CONCLUSIONS:
Plasma DA:NE and DOPAC:DHPG ratios are remarkably sensitive and specific for diagnosing Menkes disease in at-risk newborns. Affected newborns also have elevated DOPA and EPI:NE ratios, which decreased DBH activity alone cannot explain.
AuthorsDavid S Goldstein, Courtney S Holmes, Stephen G Kaler
JournalNeurochemical research (Neurochem Res) Vol. 34 Issue 8 Pg. 1464-8 (Aug 2009) ISSN: 1573-6903 [Electronic] United States
PMID19234788 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Biomarkers
  • Catechols
  • 3,4-Dihydroxyphenylacetic Acid
  • Methoxyhydroxyphenylglycol
  • 3,4-dihydroxyphenylglycol
  • Dopamine
  • Norepinephrine
  • Epinephrine
Topics
  • 3,4-Dihydroxyphenylacetic Acid (blood)
  • Biomarkers
  • Catechols (blood)
  • Chromatography, High Pressure Liquid
  • Dopamine (blood)
  • Epinephrine (blood)
  • Humans
  • Infant, Newborn
  • Male
  • Menkes Kinky Hair Syndrome (blood, diagnosis, genetics)
  • Methoxyhydroxyphenylglycol (analogs & derivatives, blood)
  • Norepinephrine (blood)
  • ROC Curve

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