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

Full Abstract

BACKGROUND: 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.

Author information

Author/s: Goldstein, David S (DS); Holmes, Courtney S (CS); Kaler, Stephen G (SG);

Affiliation: Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA. goldsteind(-atsign-)ninds.nih.gov

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural

Journal: Neurochemical research (Neurochem Res), published in United States. (Language: eng)

Reference: 2009-Aug; vol 34 (issue 8) : pp 1464-8

Dates: Created 2009/06/08; Completed 2009/08/20;

PMID: 19234788, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Humans
Infant, Newborn
Male
Menkes Kinky Hair Syndrome - blood; diagnosis; genetics
Methoxyhydroxyphenylglycol - analogs & derivatives; blood
Norepinephrine - blood
ROC Curve

Associated Chemicals: Biological Markers (0) ; Catechols (0) ; 3,4-Dihydroxyphenylacetic Acid (102-32-9) ; dihydroxyphenylethylene glycol (3343-19-9) ; Norepinephrine (51-41-2) ; Epinephrine (51-43-4) ; Methoxyhydroxyphenylglycol (534-82-7)

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