A Novel Adult-Onset, Progressive MAO-A Hypofunction

Purpose We describe the clinical presentation, pathophysiology, and successful treatment of a previously undocumented adult onset, progressive form of monoamine oxidase A hypofunction. The patient experienced progressive symptoms consistent with excess intracellular noradrenaline in the sympathetic nervous system and with a reduced ability to metabolize tyramine — both associated with low monoamine oxidase A activity. Methods The hypothesis of monoamine oxidase A hypofunction was tested first by fractionated plasma catecholamine assays, performed at baseline and again following administration of entacapone, which suppresses catechol-O-methyltransferase function. Plasma noradrenaline levels are unaffected by entacapone in healthy adults, due to monoamine oxidase A activity. This test was followed by a direct measurement of plasma catechols (specifically metabolites of norepinephrine and dopamine), to compare their respective levels and ratios to known cases of X-linked monoamine oxidase A microdeletion. Results Under the entacapone challenge, the patient’s plasma noradrenaline increased by 89%, consistent with monoamine oxidase A hypofunction. When repeated with daily rasagiline administration, the increase fell to 14%. Further challenges showed a variable but consistent increase under entacapone. Catecholamine measurement showed that levels of dihydroxyphenylglycol, a metabolite of norepinephrine via monoamine oxidase A, and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine via monoamine oxidase A, were significantly below reference range. Treatment consistent with the hypothesis consisted of rasagiline or selegiline combined with carvedilol and relieved all symptoms. Conclusion Here we characterize a novel, progressive, adult-onset form of monoamine oxidase A hypofunction in a previously healthy man.