Thiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation

Thiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation | 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 Case Report Thiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation Yathwin Kanagavel Malmurugan, Ganga Pujitha Immanni, Umapathy Pasupathy, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4556014/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Thiamine metabolism dysfunction syndrome type-4 (THMD-4) is an exceptionally rare autosomal recessive neuro-metabolic disorder characterized by febrile illness-associated episodic encephalopathy, bilateral striatal necrosis, and progressive polyneuropathy. It is caused by bi-allelic pathogenic variations in the SLC25A19 gene encoding the mitochondrial thiamine pyrophosphate carrier. THMD-4 typically presents with recurrent episodes of encephalopathy and weakness triggered by febrile illness, posing diagnostic challenges due to its rarity and variable clinical manifestations. Case Presentation : We report the case of an 8-year-old boy, developmentally normal, presenting with weakness in all four limbs following a febrile episode. Notably, the patient lacked altered sensorium. Clinical examination revealed distal muscle weakness, abnormal gait, and absent deep tendon reflexes. Neuroimaging demonstrated characteristic bilateral basal ganglia lesions. Genetic testing identified bi-allelic pathogenic variants in SLC25A19, confirming the diagnosis of THMD-4. Treatment with high-dose biotin and thiamine resulted in gradual improvement of weakness. Conclusion This case highlights an unusual presentation of THMD-4 characterized by the absence of typical encephalopathic features. Despite the atypical clinical manifestation, characteristic imaging findings and genetic testing enabled definitive diagnosis. Early recognition of diverse presentations of THMD-4 is crucial for timely intervention and prevention of neurological sequelae. Increased awareness among clinicians about the variable clinical spectrum of THMD-4 can facilitate prompt diagnosis and optimize patient outcomes. Inborn errors of metabolism thiamine encephalopathy genetic disorder Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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-4556014","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":317198780,"identity":"70a24658-6009-4069-b21c-6e8bf89f086c","order_by":0,"name":"Yathwin Kanagavel Malmurugan","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Yathwin","middleName":"Kanagavel","lastName":"Malmurugan","suffix":""},{"id":317198781,"identity":"8aafa736-cb87-4c84-b1dd-a34e7bccfd6c","order_by":1,"name":"Ganga Pujitha Immanni","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Ganga","middleName":"Pujitha","lastName":"Immanni","suffix":""},{"id":317198782,"identity":"0f91c334-fd9f-4653-9d32-4f6d33f25e40","order_by":2,"name":"Umapathy Pasupathy","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Umapathy","middleName":"","lastName":"Pasupathy","suffix":""},{"id":317198783,"identity":"ea857e94-d14e-4415-a97a-7d9a9d4796c3","order_by":3,"name":"Rajeswaran Rangasami","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Rajeswaran","middleName":"","lastName":"Rangasami","suffix":""},{"id":317198784,"identity":"eb2a30ee-cfe3-4747-91dd-cc176642532a","order_by":4,"name":"Dinesh Kumar Jayapalan","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Dinesh","middleName":"Kumar","lastName":"Jayapalan","suffix":""},{"id":317198785,"identity":"829156a3-7fe7-4fa4-b6bf-d16dfb7bd79b","order_by":5,"name":"Ranjith Kumar Manokaran","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYDCCA1CasZmBjeEDkMHGTlgLYwNECzMb4wyQFmZitTAwMLMx84BpAjr4jjc/f8C4xy6PuZ3/2GObX9vk+ZgZGD98zMGtRfLMMcMGhmfJxUCHsRvn9t02bGNmYJacuQ23FoMbOUCHHWBObAT6RTq35zYjUAsbMy9hLfUQLZY9t+2J1XIYooXhx+1EglpAfpmRcOA4SIuZZG/D7eQ2ZsZmvH4BhtiDDx8OVCdu7D/4TOLHn9u289ubD374iEcLGCQAMTDcgPHZBuLCIooQkAeTf4hTPApGwSgYBSMLAAAAelDIBVy0HQAAAABJRU5ErkJggg==","orcid":"","institution":"Sri Ramachandra Institute of Higher Education and Research","correspondingAuthor":true,"prefix":"","firstName":"Ranjith","middleName":"Kumar","lastName":"Manokaran","suffix":""}],"badges":[],"createdAt":"2024-06-10 05:55:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4556014/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4556014/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85189407,"identity":"e908182b-1f8a-4a69-ad84-8beaffac81dc","added_by":"auto","created_at":"2025-06-23 08:39:26","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":373347,"visible":true,"origin":"","legend":"","description":"","filename":"THMD4BMC1strevision1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4556014/v1_covered_12053508-3999-467d-a81b-cc41b7e11f3b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"Inborn errors of metabolism, thiamine, encephalopathy, genetic disorder","lastPublishedDoi":"10.21203/rs.3.rs-4556014/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4556014/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThiamine metabolism dysfunction syndrome type-4 (THMD-4) is an exceptionally rare autosomal recessive neuro-metabolic disorder characterized by febrile illness-associated episodic encephalopathy, bilateral striatal necrosis, and progressive polyneuropathy. It is caused by bi-allelic pathogenic variations in the SLC25A19 gene encoding the mitochondrial thiamine pyrophosphate carrier. THMD-4 typically presents with recurrent episodes of encephalopathy and weakness triggered by febrile illness, posing diagnostic challenges due to its rarity and variable clinical manifestations.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003e: We report the case of an 8-year-old boy, developmentally normal, presenting with weakness in all four limbs following a febrile episode. Notably, the patient lacked altered sensorium. Clinical examination revealed distal muscle weakness, abnormal gait, and absent deep tendon reflexes. Neuroimaging demonstrated characteristic bilateral basal ganglia lesions. Genetic testing identified bi-allelic pathogenic variants in SLC25A19, confirming the diagnosis of THMD-4. Treatment with high-dose biotin and thiamine resulted in gradual improvement of weakness.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case highlights an unusual presentation of THMD-4 characterized by the absence of typical encephalopathic features. Despite the atypical clinical manifestation, characteristic imaging findings and genetic testing enabled definitive diagnosis. Early recognition of diverse presentations of THMD-4 is crucial for timely intervention and prevention of neurological sequelae. Increased awareness among clinicians about the variable clinical spectrum of THMD-4 can facilitate prompt diagnosis and optimize patient outcomes.\u003c/p\u003e","manuscriptTitle":"Thiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-27 10:13:17","doi":"10.21203/rs.3.rs-4556014/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":"241d418b-6673-4507-9f05-2184b0033ad2","owner":[],"postedDate":"June 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-23T08:39:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-27 10:13:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4556014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4556014","identity":"rs-4556014","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}