Research & Literature

Leigh syndrome: Resolving the clinical and genetic heterogeneity paves the way for treatment options.

Gerards M, Sallevelt SC, Smeets HJ

Molecular genetics and metabolism 2016; (117(3)):300-12.

The neuroimaging of Leigh syndrome: case series and review of the literature.

Bonfante E, Koenig MK, Adejumo RB, et al.

Pediatric radiology 2016; (46(4)):443-51 doi:10.1007/s00247-015-3523-5.

Ndufs4 related Leigh syndrome: A case report and review of the literature.

Ortigoza-Escobar JD, Oyarzabal A, Montero R, et al.

Mitochondrion 2016; (28()):73-8.

Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease.

Martikainen MH, Ng YS, Gorman GS, et al.

JAMA neurology 2016; (73(6)):668-74 doi:10.1001/jamaneurol.2016.0355.

Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients.

Kuperberg M, Lev D, Blumkin L, et al.

Journal of child neurology 2016; (31(14)):1534-1539 doi:10.1177/0883073816664836.

Schizophrenia-like symptoms in a patient with Leigh syndrome.

Satogami K, Takahashi S, Kose A, Shinosaki K

Asian journal of psychiatry 2017; (25()):249-250 doi:10.1016/j.ajp.2016.12.012.

Associations of quality of life with health-related characteristics among children with autism.

Kuhlthau KA, McDonnell E, Coury DL, et al.

Autism : the international journal of research and practice 2018; (22(7)):804-813 doi:10.1177/1362361317704420.

Pediatric mitochondrial diseases and the heart.

Enns GM

Current opinion in pediatrics 2017; (29(5)):541-551 doi:10.1097/MOP.0000000000000535.

Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature.

Chourasia N, Adejumo RB, Patel RP, Koenig MK

Pediatric neurology 2017; (74()):97-99 doi:10.1016/j.pediatrneurol.2017.05.008.

Japanese Leigh syndrome case treated with EPI-743.

Kouga T, Takagi M, Miyauchi A, et al.

Brain & development 2018; (40(2)):145-149 doi:10.1016/j.braindev.2017.08.005.

Do parents and children agree on rating a child's HRQOL? A systematic review and Meta-analysis of comparisons between children with attention deficit hyperactivity disorder and children with typical development using the PedsQLTM.

Lee YC, Yang HJ, Lee WT, Teng MJ

Disability and rehabilitation 2019; (41(3)):265-275 doi:10.1080/09638288.2017.1391338.

Anesthetic Management in Mitochondrial Encephalomyopathy: A Case Report.

Yamamoto T, Miyazawa N, Yamamoto S, Kawahara H

Anesthesia progress 2017; (64(4)):235-239 doi:10.2344/anpr-64-03-06.

Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome.

Maalej M, Kammoun T, Alila-Fersi O, et al.

Biochemical and biophysical research communications 2018; (497(4)):1043-1048 doi:10.1016/j.bbrc.2018.02.169.

Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family.

Weerasinghe CAL, Bui BT, Vu TT, et al.

Molecular medicine reports 2018; (17(5)):6919-6925 doi:10.3892/mmr.2018.8670.

Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome.

Uittenbogaard M, Brantner CA, Fang Z, et al.

Molecular genetics and metabolism 2018; (124(1)):71-81 doi:10.1016/j.ymgme.2018.03.011.

Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients.

Danis D, Brennerova K, Skopkova M, et al.

Endocrine regulations 2018; (52(2)):110-118.

A Novel NDUFS3 mutation in a Chinese patient with severe Leigh syndrome.

Lou X, Shi H, Wen S, et al.

Journal of human genetics 2018; (63(12)):1269-1272 doi:10.1038/s10038-018-0505-0.

[An interpretation of the expert consensus on standards for the management of patients with primary mitochondrial disease from the Mitochondrial Medicine Society].

Guo Y, Hong SQ, Jiang L

Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2018; (20(11)):887-892.

Fatigue in young people with Duchenne muscular dystrophy.

El-Aloul B, Speechley KN, Wei Y, et al.

Developmental medicine and child neurology 2020; (62(2)):245-251 doi:10.1111/dmcn.14248.

[Paroxysmal crying and motor regression for more than two months in an infant].

Wen YX, Wang JP, Chen Y, Bao XH

Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2019; (21(4)):399-404.

Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians.

Paik K, Lines MA, Chakraborty P, et al.

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 2019; (46(6)):717-726 doi:10.1017/cjn.2019.240.

Mortality of Japanese patients with Leigh syndrome: Effects of age at onset and genetic diagnosis.

Ogawa E, Fushimi T, Ogawa-Tominaga M, et al.

Journal of inherited metabolic disease 2020; (43(4)):819-826 doi:10.1002/jimd.12218.

A meta-analysis and systematic review of Leigh syndrome: clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations.

Chang X, Wu Y, Zhou J, et al.

Medicine 2020; (99(5)):e18634 doi:10.1097/MD.0000000000018634.

Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease.

Friederich MW, Elias AF, Kuster A, et al.

Journal of inherited metabolic disease 2020; (43(5)):1024-1036 doi:10.1002/jimd.12232.

Clinical Characteristics of Early-Onset and Late-Onset Leigh Syndrome.

Hong CM, Na JH, Park S, Lee YM

Frontiers in neurology 2020; (11()):267 doi:10.3389/fneur.2020.00267.

Cerebellar stroke-like lesions in Leigh syndrome may mimic cerebellar cortical bleeding.

Finsterer J

eNeurologicalSci 2020; (19()):100234 doi:10.1016/j.ensci.2020.100234.

Fatal cerebellar oedema in adult Leigh syndrome.

Edwards LS, Halmagyi GM, Mallawaarachchi A, et al.

Practical neurology 2020; (20(4)):336-337 doi:10.1136/practneurol-2019-002409.

Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: case report of an Italian patient.

Piro E, Serra G, Antona V, et al.

Italian journal of pediatrics 2020; (46(1)):140 doi:10.1186/s13052-020-00903-7.

Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines.

Barcelos I, Shadiack E, Ganetzky RD, Falk MJ

Current opinion in pediatrics 2020; (32(6)):707-718 doi:10.1097/MOP.0000000000000954.

Complex I deficiency and Leigh syndrome through the eyes of a clinician.

Reinson K, Õunap K

EMBO molecular medicine 2020; (12(11)):e13187 doi:10.15252/emmm.202013187.

Management considerations for stroke-like episodes in MELAS with concurrent COVID-19 infection.

Sen K, Harrar D, Hahn A, et al.

Journal of neurology 2021; (268(11)):3988-3991 doi:10.1007/s00415-021-10538-1.

Ptosis, ophthalmoplegia and corneal endothelial disease - ocular manifestations of mitochondrial disease.

McElnea EM, Pick ZS, Smyth AC, et al.

American journal of ophthalmology case reports 2021; (22()):101073 doi:10.1016/j.ajoc.2021.101073.

Homoplasmy of the m. 8993 T>G variant in a patient without MRI findings of Leigh syndrome, ataxia or retinal abnormalities.

Saneto RP, Patrick KE, Perez FA

Mitochondrion 2021; (59()):58-62 doi:10.1016/j.mito.2021.04.010.

Leigh Syndrome and SURF1 Gene Presenting with Febrile Seizure.

Panda PK, Sharawat IK, Sharma V, Sherwani P

Annals of Indian Academy of Neurology 2021; (24(2)):251-252 doi:10.4103/aian.AIAN_567_20.

Adeno-associated viral vector serotype 9-based gene replacement therapy for SURF1-related Leigh syndrome.

Ling Q, Rioux M, Hu Y, et al.

Molecular therapy. Methods & clinical development 2021; (23()):158-168 doi:10.1016/j.omtm.2021.09.001.

Leigh syndrome in an infant: autopsy and histopathology findings.

Saini AG, Chatterjee D, Bhagwat C, et al.

Autopsy & case reports 2021; (11()):e2021334 doi:10.4322/acr.2021.334.

Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.

van de Wal MAE, Adjobo-Hermans MJW, Keijer J, et al.

Brain : a journal of neurology 2022; (145(1)):45-63 doi:10.1093/brain/awab426.

Differential effects of mTOR inhibition and dietary ketosis in a mouse model of subacute necrotizing encephalomyelopathy.

Bornstein R, James K, Stokes J, et al.

Neurobiology of disease 2022; (163()):105594 doi:10.1016/j.nbd.2021.105594.

Development of Leigh syndrome with a high probability of cardiac manifestations in infantile-onset patients with m.14453G > A.

Shimura M, Onuki T, Sugiyama Y, et al.

Mitochondrion 2022; (63()):1-8 doi:10.1016/j.mito.2021.12.005.

Expression signature of the Leigh syndrome French-Canadian type.

Bchetnia M, Tardif J, Morin C, Laprise C

Molecular genetics and metabolism reports 2022; (30()):100847 doi:10.1016/j.ymgmr.2022.100847.

Novel NARS2 variant causing leigh syndrome with normal lactate levels.

Tanaka R, Takeguchi R, Kuroda M, et al.

Human genome variation 2022; (9(1)):12 doi:10.1038/s41439-022-00191-z.

Biotin-Responsive Basal Ganglia Disease: Treatable Metabolic Disorder with SLC19A3 Mutation Presenting as Rapidly Progressive Dementia.

Oommen AT, Polavarapu K, Christopher R, Netravathi M

Neurology India 2022; (70(2)):733-736 doi:10.4103/0028-3886.344659.

Endocrine Manifestations and New Developments in Mitochondrial Disease.

Ng YS, Lim AZ, Panagiotou G, et al.

Endocrine reviews 2022; (43(3)):583-609 doi:10.1210/endrev/bnab036.

Screening and prevalence of cardiac abnormalities on electro- and echocardiography in a large cohort of patients with mitochondrial disease.

Hendrix CLF, van den Heuvel FMA, Rodwell L, et al.

Molecular genetics and metabolism 2022; (136(3)):219-225 doi:10.1016/j.ymgme.2022.05.004.

AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives.

Hanaford AR, Cho YJ, Nakai H

Orphanet journal of rare diseases 2022; (17(1)):217 doi:10.1186/s13023-022-02324-7.

Heteroplasmic Mutant Load Differences in Mitochondrial DNA-Associated Leigh Syndrome.

Na JH, Lee YM

Pediatric neurology 2023; (138()):27-32 doi:10.1016/j.pediatrneurol.2022.09.006.

Home Milrinone in Pediatric Hospice Care of Children with Heart Failure.

Hollander SA, Wujcik K, Schmidt J, et al.

Journal of pain and symptom management 2023; (65(3)):216-221 doi:10.1016/j.jpainsymman.2022.11.014.

Transcriptomic analyses reveal neuronal specificity of Leigh syndrome associated genes.

Wahedi A, Soondram C, Murphy AE, et al.

Journal of inherited metabolic disease 2023; (46(2)):243-260 doi:10.1002/jimd.12578.

Generation of two mother-child pairs of iPSCs from maternally inherited Leigh syndrome patients with m.8993 T > G and m.9176 T > G MT-ATP6 mutations.

Henke MT, Zink A, Diecke S, et al.

Stem cell research 2023; (67()):103030 doi:10.1016/j.scr.2023.103030.

Leigh syndrome.

Rahman S

Handbook of clinical neurology 2023; (194()):43-63 doi:10.1016/B978-0-12-821751-1.00015-4.

Case report: malignant hypertension associated with catecholamine excess in a patient with Leigh syndrome.

Solis A, Shimony J, Shinawi M, Barton KT

Clinical hypertension 2023; (29(1)):7 doi:10.1186/s40885-022-00231-4.

Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations.

Chung CCY, Hue SPY, Ng NYT, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2023; (25(9)):100896 doi:10.1016/j.gim.2023.100896.

Leigh syndrome global patient registry: uniting patients and researchers worldwide.

Zilber S, Woleben K, Johnson SC, et al.

Orphanet journal of rare diseases 2023; (18(1)):264 doi:10.1186/s13023-023-02886-0.

Schizophrenia-Like Psychotic Symptoms Associated to Leigh Syndrome.

Jaballah F, Ben Soussia Nouira R, Mallouli S, et al.

Case reports in psychiatry 2023; (2023()):8886555 doi:10.1155/2023/8886555.

Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study.

Rosina E, Pezzani L, Apuril E, et al.

Molecular genetics & genomic medicine 2024; (12(1)):e2316 doi:10.1002/mgg3.2316.

A novel mitochondrial DNA variant in MT-ND6: m.14430A>C p.(Trp82Gly) identified in a patient with Leigh syndrome and complex I deficiency.

Meldau S, Ackermann S, Riordan G, et al.

Molecular genetics and metabolism reports 2024; (39()):101078 doi:10.1016/j.ymgmr.2024.101078.

NDUFV1-Related Mitochondrial Complex-1 Disorders: A Retrospective Case Series and Literature Review.

Mahesan A, Choudhary PK, Kamila G, et al.

Pediatric neurology 2024; (155()):91-103 doi:10.1016/j.pediatrneurol.2024.02.012.

Late-Onset Leigh Syndrome With Protracted Gastrointestinal Manifestations: A Rare Case Report.

Amar Z, Hussaini H, Kachhadia MP, et al.

Cureus 2024; (16(5)):e59669 doi:10.7759/cureus.59669.

Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism.

Kanemaru E, Shimoda K, Marutani E, et al.

The Journal of clinical investigation 2024; (134(15)).

Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease.

Kayser EB, Chen Y, Mulholland M, et al.

Research square 2024; doi:10.21203/rs.3.rs-4202689/v1.

Mitochondria transfer-based therapies reduce the morbidity and mortality of Leigh syndrome.

Nakai R, Varnum S, Field RL, et al.

Nature metabolism 2024; (6(10)):1886-1896 doi:10.1038/s42255-024-01125-5.

[Leigh syndrome caused by the mitochondrial m.8993T>G mutation with hypocitrullinemia: a report of four cases and literature review].

Li YX, Wang DJ, Zhou MB, et al.

Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2024; (26(9)):940-945 doi:10.7499/j.issn.1008-8830.2404036.

Genetic analysis of 280 children with unexplained developmental delay or intellectual disability using whole exome sequencing.

Xu J, Su W, Wang Y, et al.

BMC pediatrics 2024; (24(1)):766 doi:10.1186/s12887-024-05245-5.

Biallelic variants in the NDUFAF6 cause mitochondrial respiratory complex assembly defects associated with Leigh syndrome in probands.

Zhou Y, Zeng X, Zhang L, et al.

Molecular genetics and metabolism reports 2024; (41()):101168 doi:10.1016/j.ymgmr.2024.101168.

Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings.

Oikarainen J, Hinttala R, Nayebzadeh N, et al.

Mitochondrion 2025; (81()):102007 doi:10.1016/j.mito.2025.102007.

Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis.

Shi Y, Chen B, Niu S, et al.

Orphanet journal of rare diseases 2025; (20(1)):59 doi:10.1186/s13023-025-03588-5.

The genotype/phenotype conundrum of inherited mitochondrial disorders: Insights from a survey of mtDNA mutations associated with Leigh syndrome in complex I.

Ahmadi ZA, Brandt U

Biochimica et biophysica acta. Molecular basis of disease 2025; (1871(8)):167996 doi:10.1016/j.bbadis.2025.167996.

Deep Brain Stimulation in Leigh-Like Syndrome Due to DNM1 Pathogenic Variant.

Villa-Villegas L, Lira-Jaime LG, Farías-Moreno KC, et al.

Tremor and other hyperkinetic movements (New York, N.Y.) 2025; (15()):32 doi:10.5334/tohm.1017.

Identification of novel NDUFA3 variants in a patient with mitochondrial disorders.

Sun Y, Wei X, Xiao B, et al.

Pediatric research 2026; (99(5)):1970-1979 doi:10.1038/s41390-025-04403-4.

Biallelic NDUFA9 variants cause a progressive neurodevelopmental disorder with prominent dystonia and mitochondrial complex I deficiency.

Magrinelli F, Taylor LS, Sedighzadeh S, et al.

Brain communications 2025; (7(5)):fcaf369 doi:10.1093/braincomms/fcaf369.

Mitochondrial Leigh syndrome: the state of the art.

Toutain G, Hoebeke C, Gastaldi M, et al.

Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 2025; (32(8)):509-516 doi:10.1016/j.arcped.2025.04.007.

From Congenital Torticollis to Leigh Syndrome: A Case Report of Diagnostic Evolution in an Infant.

Jeon M, Yang SS, Lee S, Choi JY

Children (Basel, Switzerland) 2025; (12(11)) doi:10.3390/children12111522.

Clinical insights into mitochondrial retinopathy: A case report on m.3243A>G mutation and macular dystrophy.

Othmani NB, Mathew S

Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society 2025; (39(4)):416-418 doi:10.4103/sjopt.sjopt_314_24.

Comprehensive Iranian guidelines for the diagnosis and management of mitochondrial disorders: an evidence- and consensus-based approach.

Dalili S, Rostampour N, Mousavi ST, et al.

Orphanet journal of rare diseases 2025; (20(1)):623 doi:10.1186/s13023-025-04127-y.

Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.

Fouché BR, Khumalo SG, Koopman WJH, Venter M

Cellular and molecular neurobiology 2026; (46(1)):42 doi:10.1007/s10571-026-01681-2.