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Relative Efficiencies of Plasma Catechol Levels and Ratios for Neonatal Diagnosis of Menkes Disease

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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 × 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 × 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.

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Abbreviations

DA:

Dopamine

DBH:

Dopamine-β-hydroxylase

DHPG:

Dihydroxyphenylglycol

DOPA:

l-3,4-Dihydroxyphenylalanine

DOPAC:

Dihydroxyphenylacetic acid

NE:

Norepinephrine

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Acknowledgments

The research reported here was supported by the intramural programs of the NINDS and NICHD.

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Authors and Affiliations

  1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10 Room 6N252, 10 Center Drive, MSC-1620, Bethesda, MD, 20892-1620, USA

    David S. Goldstein & Courtney S. Holmes

  2. Unit on Pediatric Genetics, Molecular Medicine Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Stephen G. Kaler

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  1. David S. Goldstein
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  2. Courtney S. Holmes
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  3. Stephen G. Kaler
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Correspondence to David S. Goldstein.

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Goldstein, D.S., Holmes, C.S. & Kaler, S.G. Relative Efficiencies of Plasma Catechol Levels and Ratios for Neonatal Diagnosis of Menkes Disease. Neurochem Res 34, 1464–1468 (2009). https://doi.org/10.1007/s11064-009-9933-8

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  • DOI: https://doi.org/10.1007/s11064-009-9933-8

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