Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease

Monique Ernst, Alan J. Zametkin, Daisy Pascualvaca, John A. Matochik, Graeme Eisenhofer, Dennis L. Murphy, Robert M. Cohen

Research output: Contribution to journalArticle

Abstract

Noradrenergic dysfunction and abnormality in monoamine oxidase (MAO) enzyme activity have been reported previously in Lesch-Nyhan (LN) disease. This study examines peripheral indices of adrenergic, noradrenergic, and MAO function in children and young adults with LN disease (n = 11), and healthy subjects (n = 9). Blood samples, collected in identical conditions prior to a positron emission tomography (PET) study, were assayed for concentrations of epinephrine (EPI), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (DHPG) (which results from the degradation of NE by monoamine oxidase type A [MAO-A]). The LN subjects had significantly higher EPI levels by 245% (p <.00) and lower DHPG levels by 42% (p <.00) compared to the control group. No group differences were noted in NE plasma levels. Cognitive function (IQ tested by Stanford Binet Intelligence Scale) was associated with EPI in the LN group (r = 0.77, p = .009), but not in the control group. The abnormally high EPI plasma concentrations may indicate another biochemical dysfunction secondary to the absence of the HPRT enzyme in LN patients. Such a biochemical deficit is likely to originate from the adrenal medulla, which is the primary site of EPI synthesis. The adrenal medulla may be directly affected by the absence of hypoxanthine guanine phosphoribosyl transferase (HPRT) enzyme, or may receive inappropriately high descending activation input from the brain. The abnormally low DHPG levels, in the context of normal NE levels, indicates low MAO activity, either as a primary deficit, or as secondary adaptive changes to spare NE levels that would otherwise be too low for adequate noradrenergic function.

Original languageEnglish (US)
Pages (from-to)320-326
Number of pages7
JournalNeuropsychopharmacology
Volume22
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

Fingerprint

Lesch-Nyhan Syndrome
Adrenergic Agents
Epinephrine
Monoamine Oxidase
Norepinephrine
Hypoxanthine
Adrenal Medulla
Guanine
Transferases
Enzymes
Control Groups
Intelligence
Positron-Emission Tomography
Cognition
Young Adult
Healthy Volunteers
Brain
dihydroxyphenylethylene glycol

Keywords

  • Aggression
  • DHPG
  • Epinephrine
  • HPRT
  • Lesch-Nyhan disease
  • Self-injurious behaviour

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ernst, M., Zametkin, A. J., Pascualvaca, D., Matochik, J. A., Eisenhofer, G., Murphy, D. L., & Cohen, R. M. (2000). Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease. Neuropsychopharmacology, 22(3), 320-326. https://doi.org/10.1016/S0893-133X(99)00119-0

Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease. / Ernst, Monique; Zametkin, Alan J.; Pascualvaca, Daisy; Matochik, John A.; Eisenhofer, Graeme; Murphy, Dennis L.; Cohen, Robert M.

In: Neuropsychopharmacology, Vol. 22, No. 3, 03.2000, p. 320-326.

Research output: Contribution to journalArticle

Ernst, M, Zametkin, AJ, Pascualvaca, D, Matochik, JA, Eisenhofer, G, Murphy, DL & Cohen, RM 2000, 'Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease', Neuropsychopharmacology, vol. 22, no. 3, pp. 320-326. https://doi.org/10.1016/S0893-133X(99)00119-0
Ernst M, Zametkin AJ, Pascualvaca D, Matochik JA, Eisenhofer G, Murphy DL et al. Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease. Neuropsychopharmacology. 2000 Mar;22(3):320-326. https://doi.org/10.1016/S0893-133X(99)00119-0
Ernst, Monique ; Zametkin, Alan J. ; Pascualvaca, Daisy ; Matochik, John A. ; Eisenhofer, Graeme ; Murphy, Dennis L. ; Cohen, Robert M. / Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease. In: Neuropsychopharmacology. 2000 ; Vol. 22, No. 3. pp. 320-326.
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abstract = "Noradrenergic dysfunction and abnormality in monoamine oxidase (MAO) enzyme activity have been reported previously in Lesch-Nyhan (LN) disease. This study examines peripheral indices of adrenergic, noradrenergic, and MAO function in children and young adults with LN disease (n = 11), and healthy subjects (n = 9). Blood samples, collected in identical conditions prior to a positron emission tomography (PET) study, were assayed for concentrations of epinephrine (EPI), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (DHPG) (which results from the degradation of NE by monoamine oxidase type A [MAO-A]). The LN subjects had significantly higher EPI levels by 245{\%} (p <.00) and lower DHPG levels by 42{\%} (p <.00) compared to the control group. No group differences were noted in NE plasma levels. Cognitive function (IQ tested by Stanford Binet Intelligence Scale) was associated with EPI in the LN group (r = 0.77, p = .009), but not in the control group. The abnormally high EPI plasma concentrations may indicate another biochemical dysfunction secondary to the absence of the HPRT enzyme in LN patients. Such a biochemical deficit is likely to originate from the adrenal medulla, which is the primary site of EPI synthesis. The adrenal medulla may be directly affected by the absence of hypoxanthine guanine phosphoribosyl transferase (HPRT) enzyme, or may receive inappropriately high descending activation input from the brain. The abnormally low DHPG levels, in the context of normal NE levels, indicates low MAO activity, either as a primary deficit, or as secondary adaptive changes to spare NE levels that would otherwise be too low for adequate noradrenergic function.",
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