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. The nature of the pathophysiology was then tested first by fractionated plasma catecholamine assays, performed at baseline and again using entacapone challenge to suppress catechol-O-methyltransferase function. Plasma noradrenaline levels are unaffected by entacapone in healthy adults, due to monoamine oxidase A activity. This 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. 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. Direct measurement of catechols 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, consistent with reduced monoamine oxidase A activity. Treatment consistent with the hypothesis consisted of rasagiline or selegiline combined with carvedilol. This treatment relieved all symptoms.
Berteau et al. (Wed,) studied this question.