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Mitochondrial DNA depletion syndrome

MedGen UID:
452449
Concept ID:
C0342782
Disease or Syndrome
Synonym: mitochondrial DNA depletion
SNOMED CT: Depletion of mitochondrial deoxyribonucleic acid (237995002); Depletion of mitochondrial DNA (237995002)
 
Monarch Initiative: MONDO:0018158
OMIM® Phenotypic series: PS603041
Orphanet: ORPHA35698

Definition

A clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mitochondrial DNA copy number in affected tissues without mutations or rearrangements in the mitochondrial DNA. It is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). Additional phenotypes include fatal infantile lactic acidosis with methylmalonic aciduria, spastic ataxia (early-onset spastic ataxia-neuropathy syndrome), and Alpers syndrome. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMitochondrial DNA depletion syndrome
Follow this link to review classifications for Mitochondrial DNA depletion syndrome in Orphanet.

Professional guidelines

PubMed

Han X, Li H, Deng J, Zhuo X, Liu Z, Xu M, Feng W, Chen S, Fang F
Neurol Sci 2024 Nov;45(11):5465-5480. Epub 2024 Jun 4 doi: 10.1007/s10072-024-07586-6. PMID: 38831166
Amtmann D, Gammaitoni AR, Galer BS, Salem R, Jensen MP
Mitochondrion 2023 Jan;68:1-9. Epub 2022 Oct 29 doi: 10.1016/j.mito.2022.10.003. PMID: 36374792

Recent clinical studies

Etiology

Chen Y, Jiao D, Liu Y, Xu X, Wang Y, Luo X, Saiyin H, Li Y, Gao K, Chen Y, Zhao SM, Ma L, Wang C
Cell Death Differ 2023 Oct;30(10):2351-2363. Epub 2023 Aug 11 doi: 10.1038/s41418-023-01205-1. PMID: 37568009Free PMC Article
Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
Vara R, Pinon M, Fratter C, Hegarty R, Hadzic N
J Inherit Metab Dis 2023 Jul;46(4):634-648. Epub 2023 May 28 doi: 10.1002/jimd.12633. PMID: 37204315
Guo J, Duan L, He X, Li S, Wu Y, Xiang G, Bao F, Yang L, Shi H, Gao M, Zheng L, Hu H, Liu X
Adv Sci (Weinh) 2021 May;8(10):2004680. Epub 2021 Mar 8 doi: 10.1002/advs.202004680. PMID: 34026460Free PMC Article
Suomalainen A, Isohanni P
Neuromuscul Disord 2010 Jul;20(7):429-37. Epub 2010 May 4 doi: 10.1016/j.nmd.2010.03.017. PMID: 20444604

Diagnosis

Samanta A, Srivastava A, Mandal K, Sarma MS, Poddar U
Indian J Gastroenterol 2023 Aug;42(4):569-574. Epub 2023 Feb 8 doi: 10.1007/s12664-022-01281-0. PMID: 36753038
Hong KT, Lim BC, Moon JS, Ko JS
Korean J Gastroenterol 2021 May 25;77(5):248-252. doi: 10.4166/kjg.2020.170. PMID: 34035203
Guo J, Duan L, He X, Li S, Wu Y, Xiang G, Bao F, Yang L, Shi H, Gao M, Zheng L, Hu H, Liu X
Adv Sci (Weinh) 2021 May;8(10):2004680. Epub 2021 Mar 8 doi: 10.1002/advs.202004680. PMID: 34026460Free PMC Article
de Barcelos IP, Emmanuele V, Hirano M
Curr Opin Neurol 2019 Oct;32(5):715-721. doi: 10.1097/WCO.0000000000000743. PMID: 31408013Free PMC Article
Remtulla S, Emilie Nguyen CT, Prasad C, Campbell C
Pediatr Neurol 2019 Jan;90:61-65. Epub 2018 Aug 9 doi: 10.1016/j.pediatrneurol.2018.08.007. PMID: 30391088

Therapy

Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
de Barcelos IP, Emmanuele V, Hirano M
Curr Opin Neurol 2019 Oct;32(5):715-721. doi: 10.1097/WCO.0000000000000743. PMID: 31408013Free PMC Article
Vita G, Vita GL, Musumeci O, Rodolico C, Messina S
Neurol Sci 2019 Apr;40(4):671-681. Epub 2019 Feb 25 doi: 10.1007/s10072-019-03764-z. PMID: 30805745
Hirano M, Emmanuele V, Quinzii CM
Essays Biochem 2018 Jul 20;62(3):467-481. doi: 10.1042/EBC20170114. PMID: 29980632Free PMC Article
Priego EM, Karlsson A, Gago F, Camarasa MJ, Balzarini J, Pérez-Pérez MJ
Curr Pharm Des 2012;18(20):2981-94. doi: 10.2174/138161212800672787. PMID: 22571666

Prognosis

Samanta A, Srivastava A, Mandal K, Sarma MS, Poddar U
Indian J Gastroenterol 2023 Aug;42(4):569-574. Epub 2023 Feb 8 doi: 10.1007/s12664-022-01281-0. PMID: 36753038
Hirano M, Berardo A, Barca E, Emmanuele V, Quinzii C, Simpson CV, Engelstad K, Rosales XQ, Thompson JLP
J Inherit Metab Dis 2021 Mar;44(2):292-300. Epub 2021 Jan 4 doi: 10.1002/jimd.12353. PMID: 33368420Free PMC Article
Shimura M, Kuranobu N, Ogawa-Tominaga M, Akiyama N, Sugiyama Y, Ebihara T, Fushimi T, Ichimoto K, Matsunaga A, Tsuruoka T, Kishita Y, Umetsu S, Inui A, Fujisawa T, Tanikawa K, Ito R, Fukuda A, Murakami J, Kaji S, Kasahara M, Shiraki K, Ohtake A, Okazaki Y, Murayama K
Orphanet J Rare Dis 2020 Jul 24;15(1):169. doi: 10.1186/s13023-020-01441-5. PMID: 32703289Free PMC Article
Keshavan N, Abdenur J, Anderson G, Assouline Z, Barcia G, Bouhikbar L, Chakrapani A, Cleary M, Cohen MC, Feillet F, Fratter C, Hauser N, Jacques T, Lam A, McCullagh H, Phadke R, Rötig A, Sharrard M, Simon M, Smith C, Sommerville EW, Taylor RW, Yue WW, Rahman S
Genet Med 2020 Jan;22(1):199-209. Epub 2019 Aug 29 doi: 10.1038/s41436-019-0613-z. PMID: 31462754
Remtulla S, Emilie Nguyen CT, Prasad C, Campbell C
Pediatr Neurol 2019 Jan;90:61-65. Epub 2018 Aug 9 doi: 10.1016/j.pediatrneurol.2018.08.007. PMID: 30391088

Clinical prediction guides

Gao K, Chen Y, Mo R, Wang C
Autophagy 2024 Feb;20(2):460-462. Epub 2024 Jan 25 doi: 10.1080/15548627.2023.2274260. PMID: 37876279Free PMC Article
Chen Y, Jiao D, Liu Y, Xu X, Wang Y, Luo X, Saiyin H, Li Y, Gao K, Chen Y, Zhao SM, Ma L, Wang C
Cell Death Differ 2023 Oct;30(10):2351-2363. Epub 2023 Aug 11 doi: 10.1038/s41418-023-01205-1. PMID: 37568009Free PMC Article
Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
Samanta A, Srivastava A, Mandal K, Sarma MS, Poddar U
Indian J Gastroenterol 2023 Aug;42(4):569-574. Epub 2023 Feb 8 doi: 10.1007/s12664-022-01281-0. PMID: 36753038
Kodani A, Yamaguchi M, Itoh R, Huynh MA, Yoshida H
Sci Rep 2022 Dec 31;12(1):22632. doi: 10.1038/s41598-022-27329-x. PMID: 36587049Free PMC Article

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