A Novel Adult-Onset, Progressive MAO-A Hypofunction

A Novel Adult-Onset, Progressive MAO-A Hypofunction | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Novel Adult-Onset, Progressive MAO-A Hypofunction Stefan Berteau, Erik Armitano This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6711491/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract 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. Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6711491","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":489921154,"identity":"151a125e-dc67-4181-b411-d694f7ed332d","order_by":0,"name":"Stefan 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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.\u0026nbsp; 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. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults 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%.\u0026nbsp; 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.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion Here we characterize a novel, progressive, adult-onset form of monoamine oxidase A hypofunction in a previously healthy man.\u003c/p\u003e","manuscriptTitle":"A Novel Adult-Onset, Progressive MAO-A Hypofunction","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-11-19 20:23:05","doi":"10.21203/rs.3.rs-6711491/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2025-07-23 18:05:02","doi":"10.21203/rs.3.rs-6711491/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2b4331dd-f796-4973-8422-6cb97a327ab3","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-05T05:09:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 20:23:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-6711491","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6711491","identity":"rs-6711491","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}