Monoaminergic Effects of Folinic Acid, l-DOPA, and 5-Hydroxytryptophan in Dihydropteridine Reductase Deficiency |
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Authors: | David S. Goldstein,Si-Houn Hahn,Courtney Holmes,&dagger Cynthia Tifft,Judith Harvey-White,&Dagger Sheldon Milstein, &Dagger Seymour Kaufman |
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Affiliation: | Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke;; Human Genetics Branch, National Institute of Child Health and Human Development;; Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, Maryland;and; Children's National Medical Center, Washington, D.C., U.S.A. |
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Abstract: | Abstract: Plasma and CSF concentrations of endogenous l -DOPA, catecholamines, and metabolites of monoamines were assayed in a patient with atypical phenylketonuria due to absent dihydropteridine reductase (DHPR), before and during treatment with folinic acid, Sinemet, and 5-hydroxytryptophan. The patient had low but detectable levels of l -DOPA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) in plasma and low but detectable levels of these compounds and of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF, with approximately normal plasma and CSF levels of norepinephrine [noradrenaline (NA)]. Folinic acid treatment approximately doubled plasma levels of l -DOPA, NA, DOPAC, and DHPG, compared with values during dietary phenylalanine restriction alone. Detection of l -DOPA, catecholamines, and monoamine metabolites in this patient indicates that monoamine synthesis in humans does not absolutely require DHPR. The results are consistent with the existence of an alternative biochemical pathway, with folinic acid treatment augmenting activity along this pathway. Low plasma levels of l -DOPA, DOPAC, and DHPG may reflect decreased catecholamine synthesis and turnover in sympathetic nerves, with compensatory increases in exocytotic release normalizing plasma NA levels. |
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Keywords: | Dihydropteridine reductase Tetrahydrobiopterin Phenylketonuria Catechols DOPA Norepinephrine Dopamine Serotonin Dihydroxyphenylacetic acid Dihydroxyphenylglycol Homovanillic acid 5-Hydroxyindoleacetic acid 5-Hydroxytryptophan |
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