{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:19:59Z","timestamp":1758845999476,"version":"3.44.0"},"reference-count":7,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Mitochondrial trifunctional protein deficiency (MTPD) is an inherited disorder of fatty acid \u03b2\u2010oxidation caused by mutations in <jats:italic>HADHA<\/jats:italic> or <jats:italic>HADHB<\/jats:italic> genes. It typically presents with cardiomyopathy or hepatic failure in early childhood; however, it may rarely present in adulthood with the neuromyopathic form.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe a patient with MTPD with isolated neuropathy mimicking Charcot\u2013Marie\u2013Tooth disease (CMT) as the first and only presenting symptom. Clinical and electrophysiological examinations were conducted, including nerve conduction studies, needle electromyography, muscle and nerve biopsies. The diagnosis was confirmed with genetic testing and enzymatic analysis of cultured skin fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report a 40\u2010year\u2010old man diagnosed with axonal CMT2 in childhood. He had pes cavus and hammer toes, mild distal lower limb weakness, and loss of vibration sense with areflexia. He later developed fatigability, improved exercise tolerance with alcohol and an episode of chest infection causing neurological decompensation without evidence of rhabdomyolysis. Neurophysiology showed non\u2010length\u2010dependent axonal sensorimotor neuropathy without myopathic features. Genetic testing confirmed that he was compound heterozygous for two <jats:italic>HADHA<\/jats:italic> variants, one of them novel, and enzymatic analysis of cultured skin fibroblasts confirmed MTPD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We report a very rare isolated neuropathic phenotype of MTPD and confirm the pathogenicity of the novel variant c.1003G&gt;A, p.(Glu335Lys). This case also highlights the need for <jats:italic>HADHA<\/jats:italic> and <jats:italic>HADHB<\/jats:italic> to be included in neuropathy gene panels as MTPD may present as CMT. Given that dietary management may prevent some complications of MTPD, achieving a diagnosis early is important.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.70048","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T04:20:08Z","timestamp":1754972408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Trifunctional Protein Deficiency due to <scp><i>HADHA<\/i><\/scp> Variants Masquerading as Charcot\u2013Marie\u2013Tooth Disease"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-3154","authenticated-orcid":false,"given":"Farkhanda","family":"Qaiser","sequence":"first","affiliation":[{"name":"Department of Neurology Tallaght University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Tallaght University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Mullins","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Beaumont Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Beaumont Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7625-0482","authenticated-orcid":false,"given":"Loai","family":"Shakerdi","sequence":"additional","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders Mater Misericordiae University Hospital, Eccles St.  Dublin Ireland"},{"name":"School of Public Health University College Dublin  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James O.","family":"Byrne","sequence":"additional","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders Mater Misericordiae University Hospital, Eccles St.  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sin\u00e9ad M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Neurology Tallaght University Hospital  Dublin Ireland"},{"name":"Academic Unit of Neurology Trinity College Dublin  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10211"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10500"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12372"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.176887"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-14-125"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP301097"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0533-8"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.70048","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:49:47Z","timestamp":1758815387000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.70048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":7,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/jns.70048"],"URL":"https:\/\/doi.org\/10.1111\/jns.70048","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"type":"print","value":"1085-9489"},{"type":"electronic","value":"1529-8027"}],"subject":[],"published":{"date-parts":[[2025,8,11]]},"assertion":[{"value":"2025-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70048"}}