{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:36Z","timestamp":1753891596093,"version":"3.41.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Mitochondrial trifunctional protein (MTP) deficiency is an autosomal recessive disorder caused by impaired metabolism of long-chain fatty acids (LCFAs). Childhood and late-onset MTP deficiency is characterized by myopathy\/rhabdomyolysis and peripheral neuropathy; however, the features are unclear. A 44-year-old woman was clinically diagnosed with Charcot-Marie-Tooth disease at 3 years of age due to gait disturbance. Her activity and voluntary speech gradually decreased in her 40s. Cognitive function was evaluated and brain imaging tests were performed. The Mini-Mental State Examination and frontal assessment battery scores were 25\/30 and 10\/18, respectively, suggesting higher brain dysfunction. Peripheral nerve conduction studies revealed axonal impairments. Brain computed tomography showed significant calcification. Magnetic resonance imaging revealed an increased gadolinium contrast-enhanced signal in the white matter, suggesting demyelination of the central nervous system (CNS) due to LCFAs. The diagnosis of MTP deficiency was confirmed through genetic examination. Administration of L-carnitine and a medium-chain fatty triglyceride diet was initiated, and the progression of higher brain dysfunction was retarded within 1 year. This patient's presentation was suggestive of CNS demyelination. The presence of brain calcification, higher brain dysfunction, or gadolinium enhancement in the white matter in patients with peripheral neuropathy may be suggestive of MTP deficiency.<\/jats:p>","DOI":"10.3389\/fneur.2023.1187822","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T04:38:28Z","timestamp":1686631108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: Mitochondrial trifunctional protein deficiency caused by HADHB gene mutation (c.1175C&gt;T) characterized by higher brain dysfunction followed by neuropathy, presented gadolinium enhancement on brain imaging in an adult patient"],"prefix":"10.3389","volume":"14","author":[{"given":"Ruoyi","family":"Ishikawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nakamori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Hashiguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.ymgme.2009.07.011","article-title":"Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency","volume":"98","author":"Purevsuren","year":"2009","journal-title":"Mol Genet Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7039","DOI":"10.1073\/pnas.1801252115","article-title":"Cryo-EM structure of human mitochondrial trifunctional protein","volume":"115","author":"Liang","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B3","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1002\/jimd.12502","article-title":"Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands","volume":"45","author":"Schwantje","year":"2022","journal-title":"J Inherit Metab Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"82","DOI":"10.5692\/clinicalneurol.cn-000976","article-title":"Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease","volume":"57","author":"Yamamoto","year":"2017","journal-title":"Rinsho Shinkeigaku"},{"key":"B5","doi-asserted-by":"publisher","first-page":"694966","DOI":"10.3389\/fneur.2021.694966","article-title":"Charcot-Marie-Tooth disease with episodic rhabdomyolysis due to two novel mutations in the \u03b2 subunit of mitochondrial trifunctional protein and effective response to modified diet therapy","volume":"12","author":"Guan","year":"2021","journal-title":"Front Neurol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1002\/ajmg.a.36434","article-title":"Mutations in HADHB, which encodes the \u03b2-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy","author":"Naiki","year":"2014","journal-title":"Am J Med Genet A"},{"key":"B7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/8904_2017_37","article-title":"Peripheral neuropathy, episodic rhabdomyolysis, and hypoparathyroidism in a patient with mitochondrial trifunctional protein deficiency","volume":"38","author":"van Vliet","year":"2018","journal-title":"JIMD Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1097\/CM9.0000000000000805","article-title":"Multisystem involvement in Chinese patients with neuromyopathic phenotype of mitochondrial trifunctional protein deficiency","volume":"133","author":"Wei","year":"2020","journal-title":"Chin Med J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"170069","DOI":"10.1098\/rsob.170069","article-title":"Sphingolipids: membrane microdomains in brain development, function and neurological diseases","volume":"7","author":"Olsen","year":"2017","journal-title":"Open Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/jnc.13897","article-title":"Sulfatide species with various fatty acid chains in oligodendrocytes at different developmental stages determined by imaging mass spectrometry","volume":"140","author":"Hirahara","year":"2017","journal-title":"J Neurochem"},{"key":"B11","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.biochi.2013.11.023","article-title":"Pathophysiology of X-linked adrenoleukodystrophy","volume":"98","author":"Berger","year":"2014","journal-title":"Biochimie"},{"key":"B12","first-page":"839","article-title":"X-linked adrenoleukodystrophy: the role of contrast-enhanced MR imaging in predicting disease progression","volume":"21","author":"Melhem","year":"2000","journal-title":"AJNR Am J Neuroradiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"101116","DOI":"10.1016\/j.plipres.2021.101116","article-title":"Fatty acids and evolving roles of their proteins in neurological, cardiovascular disorders and cancers","volume":"83","author":"Mallick","year":"2021","journal-title":"Prog Lipid Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ymgmr.2015.10.015","article-title":"Mitochondrial trifunctional protein deficiency due to HADHB gene mutation in a Chinese family","volume":"5","author":"Fu","year":"2015","journal-title":"Mol Genet Metab Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"7144","DOI":"10.3390\/ijms23137144","article-title":"An altered sphingolipid profile as a risk factor for progressive neurodegeneration in long-chain 3-hydroxyacyl-CoA deficiency (LCHADD)","volume":"23","author":"Tucci","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1177\/2326409817701472","volume":"5","author":"Amaral","year":"2017","journal-title":"J Inborn Errors Meta. Screen"},{"key":"B17","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ymgme.2022.09.004","article-title":"Clinical and biochemical footprints of inherited metabolic disorders: X. Metabolic myopathies","volume":"137","author":"Angelini","year":"2022","journal-title":"Mol Genet Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1756286419843359","DOI":"10.1177\/1756286419843359","article-title":"Metabolic lipid muscle disorders: biomarkers and treatment","volume":"12","author":"Angelini","year":"2019","journal-title":"Ther Adv Neurol Disord"},{"key":"B19","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/s0950-351x(05)80068-0","article-title":"Defects of fatty-acid oxidation in muscle","volume":"4","author":"Angelini","year":"1990","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s40142-017-0125-6","article-title":"Advances in the understanding and treatment of mitochondrial fatty acid oxidation disorders","volume":"5","author":"Goetzman","year":"2017","journal-title":"Curr Genet Med Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s11154-018-9448-1","article-title":"Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle","volume":"19","author":"Knottnerus","year":"2018","journal-title":"Rev Endocr Metab Disord"},{"key":"B22","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1002\/jimd.12372","article-title":"The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein","volume":"44","author":"Gr\u00fcnert","year":"2021","journal-title":"J Inherit Metab Dis"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1187822\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T04:38:32Z","timestamp":1686631112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1187822\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,13]]},"references-count":22,"alternative-id":["10.3389\/fneur.2023.1187822"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1187822","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2023,6,13]]},"article-number":"1187822"}}