{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:23:12Z","timestamp":1777980192495,"version":"3.51.4"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Key Development Program of Children\u2019s Hospital of Fudan University","award":["EK2022ZX05"],"award-info":[{"award-number":["EK2022ZX05"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial transcription factor A (TFAM) deficiency may cause mtDNA depletion syndrome, which manifests as neonatal liver failure or primary ovarian insufficiency, hearing loss, seizures, and intellectual disability. Treatment focusing on symptomatic management, and the clinical prognosis remains poor. Here, we describe a novel case of <jats:italic>TFAM<\/jats:italic> mutation presenting with progressive neonatal cholestasis, hypoglycemia and abnormal amino acid profiling. The patient progressed to liver failure at 6\u00a0months of age but did not exhibit neurological involvement. No morphologic abnormalities were observed in muscle biopsy, while mtDNA copy number was reduced in comparison to age- and tissue-matched controls. After liver transplantation, liver biochemistries and blood amino acid profiling normalized three weeks later. Moreover, the boy was doing well post-transplant without any clinical concerns, and his development and neurological examination remain normal 33\u00a0months after liver transplantation. Our report suggests that liver transplantation appears to have a favorable profile in such patients.<\/jats:p>","DOI":"10.1186\/s13023-024-03487-1","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:07:32Z","timestamp":1734962852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Liver transplantation in a boy with TFAM mutation associated mtDNA depletion syndrome"],"prefix":"10.1186","volume":"19","author":[{"given":"Jing","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-7356","authenticated-orcid":false,"given":"Xin-bao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"issue":"9","key":"3487_CR1","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1093\/hmg\/ddh109","volume":"13","author":"MI Ekstrand","year":"2004","unstructured":"Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, et al. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet. 2004;13(9):935\u201344.","journal-title":"Hum Mol Genet"},{"issue":"9\u201310","key":"3487_CR2","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.bbagrm.2012.03.002","volume":"1819","author":"CT Campbell","year":"2012","unstructured":"Campbell CT, Kolesar JE, Kaufman BA. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta. 2012;1819(9\u201310):921\u20139.","journal-title":"Biochim Biophys Acta"},{"issue":"1\u20132","key":"3487_CR3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ymgme.2016.07.001","volume":"119","author":"AR Stiles","year":"2016","unstructured":"Stiles AR, Simon MT, Stover A, Eftekharian S, Khanlou N, Wang HL, et al. Mutations in TFAM, encoding mitochondrial transcription factor A, cause neonatal liver failure associated with mtDNA depletion. Mol Genet Metab. 2016;119(1\u20132):91\u20139.","journal-title":"Mol Genet Metab"},{"issue":"12","key":"3487_CR4","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s00439-021-02380-2","volume":"140","author":"F Ullah","year":"2021","unstructured":"Ullah F, Rauf W, Khan K, Khan S, Bell KM, de Oliveira VC, et al. A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss. Hum Genet. 2021;140(12):1733\u201351.","journal-title":"Hum Genet"},{"issue":"2","key":"3487_CR5","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s13311-013-0177-6","volume":"10","author":"AW El-Hattab","year":"2013","unstructured":"El-Hattab AW, Scaglia F. Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options. Neurotherapeutics. 2013;10(2):186\u201398.","journal-title":"Neurotherapeutics"},{"issue":"12","key":"3487_CR6","doi-asserted-by":"publisher","first-page":"6447","DOI":"10.3390\/ijms22126447","volume":"22","author":"J Ramon","year":"2021","unstructured":"Ramon J, Vila-Julia F, Molina-Granada D, Molina-Berenguer M, Melia MJ, Garcia-Arumi E, et al. Therapy prospects for mitochondrial DNA maintenance disorders. Int J Mol Sci. 2021;22(12):6447.","journal-title":"Int J Mol Sci."},{"issue":"3","key":"3487_CR7","doi-asserted-by":"publisher","DOI":"10.1111\/petr.14437","volume":"27","author":"S Holve","year":"2022","unstructured":"Holve S, Hu D. The long-term outcomes after liver transplantation in MPV-17 deficiency (Navajo Neurohepatopathy) are poor. Pediatr Transplant. 2022;27(3): e14437.","journal-title":"Pediatr Transplant."},{"issue":"1","key":"3487_CR8","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s13023-020-01441-5","volume":"15","author":"M Shimura","year":"2020","unstructured":"Shimura M, Kuranobu N, Ogawa-Tominaga M, Akiyama N, Sugiyama Y, Ebihara T, et al. Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: evaluation of outcomes after liver transplantation. Orphanet J Rare Dis. 2020;15(1):169.","journal-title":"Orphanet J Rare Dis"},{"key":"3487_CR9","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1196\/annals.1293.029","volume":"1011","author":"RK Bai","year":"2004","unstructured":"Bai RK, Perng CL, Hsu CH, Wong LJC. Quantitative PCR analysis of mitochondrial DNA content in patients with mitochondrial disease. Ann Ny Acad Sci. 2004;1011:304\u20139.","journal-title":"Ann Ny Acad Sci"},{"issue":"10","key":"3487_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2022.166467","volume":"1868","author":"M Mehmedovic","year":"2022","unstructured":"Mehmedovic M, Martucci M, Spahr H, Ishak L, Mishra A, Sanchez-Sandoval ME, et al. Disease causing mutation (P178L) in mitochondrial transcription factor A results in impaired mitochondrial transcription initiation. Biochim Biophys Acta Mol Basis Dis. 2022;1868(10): 166467.","journal-title":"Biochim Biophys Acta Mol Basis Dis"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03487-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03487-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03487-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T15:04:34Z","timestamp":1734966274000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03487-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3487"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03487-1","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]},"assertion":[{"value":"12 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committees on Human Research of the Children\u2019s Hospital of Fudan University. Informed parental consent was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors disclose no conflicts.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"486"}}