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J Neurol Sci 2020 Jul 11;414:116895. Epub 2020 May 11.

Department of Medicine/Neurology, Hamilton, Ontario, Canada; Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

J Neuroophthalmol 2020 Apr 28. Epub 2020 Apr 28.

State University of New York College of Optometry (CC), New York, New York; and Department of Ophthalmology (SWS, LRDG), Columbia University Irving Medical Center, New York, New York.

J Neuromuscul Dis 2020 ;7(3):355-360

Department of Neurology, Tallaght University Hospital, Tallaght, Dublin, Ireland.

We describe a patient with chronic progressive external ophthalmoplegia (CPEO) due to a rare mitochondrial genetic variant. Muscle biopsy revealed numerous cytochrome c oxidase (COX)-deficient fibres, prompting sequencing of the entire mitochondrial genome in muscle which revealed a rare m.12334G>A variant in the mitochondrial (mt-) tRNALeu(CUN)(MT-TL2) gene. Read More

J Neurol Sci 2020 Jun 1;413:116816. Epub 2020 Apr 1.

Department of Medicine/Neurology, McMaster University, Hamilton, Ontario, Canada; Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

Lipofuscin aggregation may result from incomplete degradation of damaged mitochondria by autophagy-lysosome pathway, and intra-mitochondrial lipofuscin aggregation may exacerbate mitochondrial abnormalities in mitochondrial myopathy (MM) and mitochondrial disease. We examined vastus lateralis muscle biopsies from 24 patients with pathologically diagnosed MM and clinically diagnosed chronic progressive external ophthalmoplegia, in comparison to the biopsies from 3 other groups:10 patients with inclusion body myositis (IBM), 11 younger adults, and 10 older subjects with no to minimal myopathic changes. Lipofuscin aggregation in muscle fibres was assessed on autofluorescence microscopy, some histochemical stains, and electron microscopy (EM). Read More

Front Neurol 2020 29;11:36. Epub 2020 Jan 29.

Key Laboratory of Primate Neurobiology, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Mitochondrial chronic progressive external ophthalmoplegia (CPEO) is a major manifestation of human mitochondrial encephalomyopathies. Previous studies have shown cognitive deficits in patients with mitochondrial diseases. However, these studies often included patients with heterogeneous subtypes of mitochondrial diseases. Read More

Rom J Morphol Embryol 2019 ;60(3):1073-1074

Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria;

Cell Rep 2019 Dec;29(12):3825-3834.e4

Friedrich Baur Institute, Department of Neurology, University of Munich, 80336 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address:

The mosaic distribution of cytochrome c oxidase (COX) and COX muscle fibers in mitochondrial disorders allows the sampling of fibers with compensated and decompensated mitochondrial function from the same individual. We apply laser capture microdissection to excise individual COX and COX fibers from the biopsies of mitochondrial myopathy patients. Using mass spectrometry-based proteomics, we quantify >4,000 proteins per patient. Read More

Dig Liver Dis 2020 01 13;52(1):1-8. Epub 2019 Dec 13.

Pediatric Clinic, Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", Baronissi, Italy. Electronic address:

Several rare pediatric liver disorders are accompanied by ophthalmic signs whose awareness and early identification may be of value in confirming/accelerating their diagnosis. Many of these signs are asymptomatic and can only be detected with an ophthalmological examination. Corneal signs are described in patients with Wilson's disease, Alagille's syndrome and some liver storage diseases. Read More

Neuroradiology 2020 02 14;62(2):133-134. Epub 2019 Dec 14.

Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, Piazza Sant'Onofrio 4, IRCCS, 00100, Rome, Italy.

Neuroradiology 2020 02 6;62(2):131-132. Epub 2019 Dec 6.

Neurological Department, Krankenanstalt Rudolfstiftung, Messerli Institute, Postfach 20, 1180, Vienna, Austria.

Surv Ophthalmol 2020 May - Jun;65(3):294-311. Epub 2019 Nov 27.

Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada. Electronic address:

Mitochondria are cellular organelles that play a key role in energy metabolism and oxidative phosphorylation. Malfunctioning of mitochondria has been implicated as the cause of many disorders with variable inheritance, heterogeneity of systems involved, and varied phenotype. Metabolically active tissues are more likely to be affected, causing an anatomic and physiologic disconnect in the treating physicians' mind between presentation and underlying pathophysiology. Read More

Transplantation 2019 12;103(12):e396

Cadiothoracic Department, University Hospital of Udine, Udine, Italy.

Curr Pharm Des 2020 ;26(1):103-109

Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Russian Federation.

Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mitochondrial encephalomyopathy, chronic progressive external ophthalmoplegia, neurogenic weakness, and Leigh syndrome. Read More

Mitochondrion 2019 11 12;49:227-231. Epub 2019 Sep 12.

Department of Pediatrics, McMaster University, Hamilton, ON, Canada. Electronic address:

Chronic progressive external ophthalmoplegia (CPEO) is a common presentation of mitochondrial disease. We performed a retrospective evaluation of the molecular genetic testing and genotype-phenotype correlations in a large cohort of adult-onset CPEO patients (N = 111). One hundred percent of patients tested had at least one mitochondrial DNA (mtDNA) deletion. Read More

Transplantation 2019 12;103(12):e395

Department of Neurology, Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria.

Neuromuscul Disord 2019 09 21;29(9):693-697. Epub 2019 Aug 21.

Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

We report a novel mitochondrial m.4414T>C variant in the mt-tRNA (MT-TM) gene in an adult patient with chronic progressive external ophthalmoplegia and myopathy whose muscle biopsy revealed focal cytochrome c oxidase (COX)-deficient and ragged red fibres. The m. Read More

PLoS One 2019 3;14(9):e0221829. Epub 2019 Sep 3.

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.

Mitochondrial DNA (mtDNA) genome integrity is essential for proper mitochondrial respiratory chain function to generate cellular energy. Nuclear genes encode several proteins that function at the mtDNA replication fork, including mitochondrial single-stranded DNA-binding protein (SSBP1), which is a tetrameric protein that binds and protects single-stranded mtDNA (ssDNA). Recently, two studies have reported pathogenic variants in SSBP1 associated with hearing loss, optic atrophy, and retinal degeneration. Read More

Curr Opin Ophthalmol 2019 Nov;30(6):476-483

Save Sight Institute, Faculty of Health and Medicine, The University of Sydney.

Purpose Of Review: Inherited myopathies, and in particular mitochondrial myopathies, are heterogeneous disorders, and ocular manifestations may be the presenting feature or offer important diagnostic clues. The ophthalmologist may be key to diagnosis, facilitating recognition of associated potentially life-threatening organ manifestations and an integral part of multidisciplinary care. This review, focusing especially on mitochondrial myopathies, provides updates on clinical features, diagnosis and recent therapeutic developments. Read More

J Chiropr Med 2019 Jun 1;18(2):144-154. Epub 2019 Jul 1.

Dr. Sid E. Williams Center for Chiropractic Research, Life University, Marietta, Georgia.

Objective: The purpose of this report is to describe care of a patient with chronic progressive external ophthalmoplegia and bilateral vestibular hypofunction.

Clinical Features: A 66-year-old patient presented with limited eye movement and mild ptosis, which led to a diagnosis of chronic progressive external ophthalmoplegia. Rotary chair testing suggested vestibular involvement. Read More

Neurosci Res 2019 Jul 23. Epub 2019 Jul 23.

Kagoshima University Graduate School of Medical and Dental Sciences, Department of Psychiatry, Kagoshima, 8-35-1 Sakuragaoka, 890-8520, Japan.

Chronic progressive external ophthalmoplegia (CPEO) is one of the most common mitochondrial disorders. It is characterized by bilateral, slowly progressing loss of extraocular muscle mobility, orbicularis oculi weakness, ptosis, and other neuromuscular symptoms, which are caused by the accumulation of multiple mitochondrial DNA (mtDNA) deletions. Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Read More

Neurol India 2019 May-Jun;67(3):920-923

Department of Neurology, Stanley Medical College, Chennai, Tamil Nadu, India.

PLoS One 2019 25;14(7):e0219628. Epub 2019 Jul 25.

Department of Neurology, Peking University First Hospital, Beijing, China.

The study aimed to evaluate the body composition of patients with mitochondrial diseases (MD) and correlate it with disease severity. Overall, 89 patients (age ≥ 18 years) with MD were recruited, including 49 with chronic progressive external ophthalmoplegia (CPEO) and 40 with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). Body composition, including fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMI), and appendicular skeletal muscle mass index (ASMI), were examined using multifrequency bioelectric impedance analysis. Read More

Transplantation 2019 12;103(12):e393-e394

Department of Cardiothoracic Science, Azienda Sanitaria Universitaria Integrata and DAME, University of Udine, Italy.

Cardiol Young 2019 Aug 4;29(8):1118-1119. Epub 2019 Jul 4.

Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria.

Rom J Morphol Embryol 2019 ;60(1):273-279

Department of Pathology, "Colentina" Clinical Hospital, Department of Molecular Biology, "Victor Babeş" National Institute for Research and Development in Pathology and Biomedical Sciences, Bucharest, Romania;

Mitochondriopathies are a heterogeneous group of genetic diseases of all ages, with a very diverse clinical presentation related to genetic heteroplasmy. The clinical symptoms display a large variability and generally, the more severe phenotypes have an early onset, even from the neonatal period, while milder ones are manifested later in the adulthood. Most publications have already demonstrated deletions or point mutations in mitochondrial deoxyribonucleic acid (DNA), but in recent years, the field of investigation has expanded to syndromes caused by mutations in the nuclear DNA (nDNA), with a Mendelian inheritance. Read More

J AAPOS 2019 10 31;23(5):295-297. Epub 2019 May 31.

Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA (mtDNA) deletion syndrome that typically presents before 20 years of age and is characterized by chronic progressive external ophthalmoplegia, pigmentary retinopathy, and a combination of cardiac conduction defects, cerebellar ataxia, and elevated cerebrospinal fluid protein levels. The mtDNA defects interfere with oxidative phosphorylation and can affect a number of cellular energy processes in various organs. We report the case of a 15-year-old girl with KSS that was uniquely associated with bilateral, symmetrical exophthalmos. Read More

Chin Med J (Engl) 2019 May;132(10):1202-1207

Department of Neurology, Peking University First Hospital, Beijing 100034, China.

Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy caused by multiple mtDNA abnormalities. There is little information about the changes of ocular fundus with CPEO. The aim of this work was to measure and evaluate changes in the macular retinal thickness and optic nerve head in patients with CPEO using spectral-domain optical coherence tomography and to compare the findings with those of healthy individuals. Read More

J Neurol Sci 2019 06 25;401:110-111. Epub 2019 Apr 25.

Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna, Austria. Electronic address:

J Pediatr Genet 2019 Jun 18;8(2):100-108. Epub 2018 Dec 18.

Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.

Biotin-thiamine responsive basal ganglia disease (BTRBGD) is an autosomal recessive neurometabolic disorder with poor genotype-phenotype correlation, caused by mutations in the gene on chromosome 2q36.6. The disease is characterized by three stages: stage 1 is a sub-acute encephalopathy often triggered by febrile illness; stage 2 is an acute encephalopathy with seizures, loss of motor function, developmental regression, dystonia, external ophthalmoplegia, dysphagia, and dysarthria; stage 3 is represented by chronic or slowly progressive encephalopathy. Read More

Ophthalmic Genet 2019 04 15;40(2):150-156. Epub 2019 Apr 15.

d Princess Haya Biotechnology Centre , Jordan University of Science and Technology , Irbid , Jordan.

Background: Horizontal gaze palsy and progressive scoliosis (HGPPS) is a rare autosomal recessive disorder due to mutations in ROBO3 gene. Patients have characteristic clinical and imaging findings. We report six patients from two families with this disorder with two novel mutations. Read More

Neuromuscul Disord 2019 05 25;29(5):358-367. Epub 2019 Feb 25.

Division of Neurochemistry, Institute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany; Department of Epileptology, University of Bonn, Germany. Electronic address:

Chronic progressive external ophthalmoplegia (CPEO) is a frequent clinical manifestation of disorders caused by pathogenic mitochondrial DNA mutations. However, for diagnostic purposes skeletal muscle tissue is used, since extraocular muscle tissue is usually not available for work-up. In the present study we aimed to identify causative factors that are responsible for extraocular muscle to be primarily affected in CPEO. Read More

Case Rep Neurol Med 2019 6;2019:5918632. Epub 2019 Mar 6.

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy.

The classic features of deoxyguanosine kinase () deficiency are infantile onset hepatic failure with nystagmus and hypotonia; mitochondrial DNA studies on affected tissue reveal mitochondrial DNA depletion. Later, it has been shown that the mutations in the same gene may present with adult-onset mitochondrial myopathy and mitochondrial DNA multiple deletions in skeletal muscle. Here we report the case of a 42-year-old Italian woman presenting with a chronic progressive external ophthalmoplegia and myopathy with mtDNA multiple deletions and the compound heterozygous c. Read More

J Neurol Sci 2019 May 29;400:145-147. Epub 2019 Mar 29.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan. Electronic address:

BMJ Case Rep 2019 Mar 31;12(3). Epub 2019 Mar 31.

Neurology Department, Centro Hospitalar de Lisboa Ocidental EPE, Lisboa, Portugal.

Mutations in the nuclear POLG1 gene compromise the integrity of mitochondrial DNA and show great allelic and clinical heterogeneity. Among adult POLG1-associated mitochondrial disease, the main clinical feature is chronic progressive external ophthalmoplegia. Other related clinical manifestations are sensory or cerebellar ataxia, peripheral neuropathy, myopathy or extrapyramidal symptoms. Read More

Neurology 2019 02;92(8):e886-e887

From the Departments of Ophthalmology (H.K.Y., J.-M.H.), Neurology (J.-Y.C., K.S.P.), and Radiology (J.H.K.), Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

Neuromuscul Disord 2019 04 11;29(4):269-273. Epub 2019 Jan 11.

Department of Neurology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

J Neurol 2019 Apr 2;266(4):953-959. Epub 2019 Feb 2.

Neurological Clinic, University of Pisa, Pisa, Italy.

Muscle pain may be part of many neuromuscular disorders including myopathies, peripheral neuropathies and lower motor neuron diseases. Although it has been reported also in mitochondrial diseases (MD), no extensive studies in this group of diseases have been performed so far. We reviewed clinical data from 1398 patients affected with mitochondrial diseases listed in the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", to assess muscle pain and its features. Read More

Neurology 2019 01;92(4):e394

From the Departments of Neurology (A.M.P., S.H.M., R.D.), Ophthalmology (M.D.A.), and Clinical Genomics (R.D.), Mayo Clinic, Scottsdale, AZ.

Nervenarzt 2019 Feb;90(2):121-130

Friedrich-Baur-Institut an der Neurologischen Klinik und Poliklinik, Klinikum der Universität München, Ziemssenstr. 1, 80336, München, Deutschland.

Mitochondrial diseases (MD) are caused by mutations in the mitochondrial DNA or nuclear DNA. The clinical manifestation is often most severe in tissues with high energy demands. The most common MDs are Leber's hereditary optic neuropathy (LHON), chronic progressive external ophthalmoplegia (CPEO) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Read More

Int J Cardiol 2019 Mar 27;279:105-111. Epub 2018 Dec 27.

Department of Pathophysiology, Oita University, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.

The most common cardiac feature of Kearns-Sayre syndrome (KSS) is atrioventricular block (AVB), and pacemaker implantations (PMIs) are recommended for KSS patients with advanced AVB. However, some KSS patients develop fatal arrhythmias such as polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and die suddenly even after PMIs. We report a patient with KSS who developed PMVT, VF, and QT prolongation, and was treated with mexiletine and successfully managed with an implantable cardioverter defibrillator (ICD). Read More

Neurology 2019 01 11;92(5):e519-e520. Epub 2019 Jan 11.

From the Department of Ophthalmology and Vision Sciences (M.T.B.N.), University of Toronto, Canada.

Adv Exp Med Biol 2018;1085:161-162

Department of Ophthalmology, Columbia University, Edward S. Harkness Eye Institute, NewYork-Presbyterian Hospital, New York, NY, USA.

Mitochondrial diseases are multisystem disorders: anemia, myopathy, lactic acidosis, CNS abnormality, endocrine abnormalities, renal disease, sensorineural deafness, and retinal involvement. The clinical abnormalities are heterogeneous, and they usually begin in childhood. Premature death occurs because of cardiac conduction defects. Read More

Mult Scler 2019 05 17;25(6):882-883. Epub 2018 Dec 17.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Mult Scler 2019 05 17;25(6):879-882. Epub 2018 Dec 17.

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA/ Harvard Medical School, Boston, MA, USA.

Evidence from genetic and pathologic studies suggests that mitochondrial dysfunction occurs in multiple sclerosis (MS). Furthermore, cases of MS have been reported in patients with mitochondrial disease. The phenotypic range of mitochondrial illness associating with MS is not yet well defined. Read More

Gene 2019 Mar 5;688:171-181. Epub 2018 Dec 5.

Department of Neurology and Paediatrics, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.

Mitochondria both produce the energy of the cell as ATP via respiration and regulate cellular metabolism. Accordingly, any deletion or mutation in the mitochondrial DNA (mtDNA) may result in a disease. One of these diseases is Kearns Sayre syndrome (KSS), described for the first time in 1958, where different large-scale deletions of different sizes and at different positions have been reported in the mitochondrial genome of patients with similar clinical symptoms. Read More

Hum Mol Genet 2019 04;28(7):1090-1099

Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Sweden.

TWINKLE is the helicase involved in replication and maintenance of mitochondrial DNA (mtDNA) in mammalian cells. Structurally, TWINKLE is closely related to the bacteriophage T7 gp4 protein and comprises a helicase and primase domain joined by a flexible linker region. Mutations in and around this linker region are responsible for autosomal dominant progressive external ophthalmoplegia (adPEO), a neuromuscular disorder associated with deletions in mtDNA. Read More

Yonsei Med J 2018 Dec;59(10):1190-1196

Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease.

Materials And Methods: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. Read More

Can J Ophthalmol 2018 10 17;53(5):e203-e205. Epub 2018 Feb 17.

Northampton General Hospital NHS Trust, Northampton, United Kingdom.