{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:07Z","timestamp":1792417387904,"version":"4.4.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial DNA maintenance defects (MDMD) are rare genetic disorders that typically present in infancy but can manifest later with multi-organ involvement. We describe four MDMD cases (age 19\u201325) with distinct clinical and genetic profiles and delayed diagnosis. Two patients with mitochondrial neurogastrointestinal encephalomyopathy (homozygous\n                    <jats:italic toggle=\"yes\">TYMP<\/jats:italic>\n                    variants: c.454G&gt;T, c.866A&gt;C) exhibited cachexia, ptosis, neuropathy, and confluent white matter hyperintensities leukodystrophy. Two others with\n                    <jats:italic toggle=\"yes\">MPV17<\/jats:italic>\n                    (c.293C&gt;T) presented with neuromyopathy and hepatosplenomegaly; one showed novel concentric ring lesions on magnetic resonance imaging (MRI). Despite severe white matter changes\/leukodystrophy, cognition was preserved. Diagnoses were delayed due to atypical gastrointestinal or neuromuscular symptoms. This series highlights the diagnostic challenge of MDMD and underscores that it should be considered in adolescents or young adults with unexplained neuropathy, white matter hyperintensities\/leukodystrophy, or cachexia, even without classic hepatic or encephalopathic features. Genetic testing is essential for diagnosis, as phenotypic variability often obscures underlying MDMD. Our findings underscore the need for increased awareness of this delayed-diagnosis presentation to enable timely intervention.\n                  <\/jats:p>","DOI":"10.4103\/aian.aian_843_25","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:00:20Z","timestamp":1767895220000},"page":"261-265","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial DNA Maintenance Defects: Clinical, Imaging, and Genetic Spectrum of Four Patients from a Single Tertiary Care Centre"],"prefix":"10.4103","volume":"29","author":[{"given":"Deepak","family":"Amalnath","sequence":"first","affiliation":[{"name":"Department of Medicine, Jawaharlal Institute of Postgraduate Institute Medical Education and Research, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayaram","family":"Saibaba","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jawaharlal Institute of Postgraduate Institute Medical Education and Research, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Wadwekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jawaharlal Institute of Postgraduate Institute Medical Education and Research, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Institute Medical Education and Research, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhakumar","family":"Senthilvelan","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Institute Medical Education and Research, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"R1-20261019","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.bbadis.2017.02.017","article-title":"Mitochondrial DNA maintenance defects","author":"El-Hattab","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"R2-20261019","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ymgme.2022.07.003","article-title":"Mitochondrial DNA maintenance defects: Potential therapeutic strategies","volume":"137","author":"Almannai","year":"2022","journal-title":"Mol Genet Metab"},{"key":"R3-20261019","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R4-20261019","doi-asserted-by":"crossref","first-page":"669","DOI":"10.3389\/fgene.2018.00669","article-title":"Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the fourth decade, what we have learned so far","volume":"9","author":"Pacitti","year":"2018","journal-title":"Front Genet"},{"key":"R5-20261019","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y","article-title":"Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations","volume":"47","author":"Nishino","year":"2000","journal-title":"Ann Neurol"},{"key":"R6-20261019","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jns.2011.06.052","article-title":"Mitochondrial neurogastrointestinal encephalopathy in an Indian family with possible manifesting carriers of heterozygous TYMP mutation","volume":"309","author":"Nalini","year":"2011","journal-title":"J Neurol Sci"},{"key":"R7-20261019","doi-asserted-by":"crossref","first-page":"310","DOI":"10.4103\/ijn.IJN_404_17","article-title":"Mitochondrial neurogastrointestinal encephalomyopathy: A nonrenal indication for peritoneal dialysis","volume":"28","author":"Chandra","year":"2018","journal-title":"Indian J Nephrol"},{"key":"R8-20261019","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/MCD.0000000000000137","article-title":"Novel sequence variations in the thymidine phosphorylase gene causing mitochondrial neurogastrointestinal encephalopathy","volume":"25","author":"Karyampudi","year":"2016","journal-title":"Clin Dysmorphol"},{"key":"R9-20261019","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1212\/WNL.0000000000002536","article-title":"Pearls and Oy-sters: Mitochondrial neurogastrointestinal encephalomyopathy: Diagnosis and response to peritoneal dialysis","volume":"86","author":"Sivadasan","year":"2016","journal-title":"Neurology"},{"key":"R10-20261019","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4103\/amhs.amhs_295_23","article-title":"An Indian Case Study on Mitochondrial Neurogastrointestinal Encephalomyopathy","volume":"12","author":"Kareem","year":"2024","journal-title":"Arch Med Health Sci"},{"key":"R11-20261019","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1136\/jnnp-2018-319481","article-title":"Practical approach to the diagnosis of adult-onset leukodystrophies: An updated guide in the genomic era","volume":"90","author":"Lynch","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R12-20261019","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/humu.23387","article-title":"MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects","volume":"39","author":"El-Hattab","year":"2018","journal-title":"Hum Mutat"},{"key":"R13-20261019","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s12098-020-03583-7","article-title":"Mitochondrial DNA depletion syndrome: Mimicker for hereditary tyrosinemia","volume":"88","author":"Kamate","year":"2021","journal-title":"Indian J Pediatr"},{"key":"R14-20261019","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s13312-014-0475-z","article-title":"Mitochondrial DNA depletion syndrome causing liver failure","volume":"51","author":"Bijarnia-Mahay","year":"2014","journal-title":"Indian Pediatr"},{"key":"R15-20261019","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mito.2017.06.006","article-title":"MPV17 hepatocerebral mitochondrial DNA depletion syndrome presenting as acute flaccid paralysis-A case report","volume":"37","author":"Pyal","year":"2017","journal-title":"Mitochondrion"},{"key":"R16-20261019","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.4103\/0028-3886.333468","article-title":"MPV17 gene variant mutation presenting as leucoencephalopathy with peripheral neuropathy","volume":"69","author":"Mundlamuri","year":"2021","journal-title":"Neurol India"},{"key":"R17-20261019","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s12664-022-01281-0","article-title":"MPV17 mutation-related mitochondrial DNA depletion syndrome: A case series in infants","volume":"42","author":"Samanta","year":"2023","journal-title":"Indian J Gastroenterol"},{"key":"R18-20261019","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s13224-023-01770-y","article-title":"Newborn genetic screening: Significance in early diagnosis of an infant with mitochondrial DNA depletion syndrome-6","volume":"74","author":"Gupte","year":"2023","journal-title":"J Obstet Gynaecol India"},{"key":"R19-20261019","doi-asserted-by":"crossref","DOI":"10.1016\/j.jceh.2024.102287","article-title":"MPV 17 Mitochondrial DNA depletion syndrome-A case series","volume":"14","author":"Bharathi","year":"2024","journal-title":"J Clin Exp Hepatol"}],"container-title":["Annals of Indian Academy of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_843_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:01:22Z","timestamp":1792414882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_843_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aian.aian_843_25","relation":{},"ISSN":["0972-2327","1998-3549"],"issn-type":[{"value":"0972-2327","type":"print"},{"value":"1998-3549","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"assertion":[{"value":"2025-08-15","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}