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Episodic Mitochondrial Myopathy - Optic Atrophy - Reversible Leukoencephalopathy


Mitochondrial myopathy is a term representing a group of disorders that arise from mutations in both nuclear and mitochondrial DNA. Several distinct syndromes have been described in the literature, the most important examples being progressive external ophthalmoplegia, and mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome. The diagnosis mandates a thorough clinical and imaging investigations, but muscle biopsies and genetic studies are required to confirm clinical suspicion and determine the exact type of myopathy.


Signs and symptoms of mitochondrial myopathies stem from defects of mitochondrial function. As these organelles are crucial for the production of energy from the respiratory chain, mutations that affect this step inevitably affect tissues that strongly depend on it - the muscles, the nervous system, the heart, and the endocrine system [1]. As a result, the clinical presentation often encompasses multiple findings [1] [2] [3] [4] [5]:

Other important manifestations include defects of the kidneys and the heart (the development of conduction deficits and cardiomyopathies, more commonly of hypertrophic type) [1] [5]. In some cases, neuropsychiatric symptoms of depression and psychotic-like syndromes are reported [1] [5].

  • On POD13, he presented to an outlying emergency department with cyanosis and poor respiratory drive. Before intubation, he received a depolarizing muscle relaxation; cardiac arrest ensued and resuscitation was unsuccessful.[ncbi.nlm.nih.gov]
Cutaneous Manifestation
  • In contrast, cutaneous manifestations are rare and are non-specific, most commonly presenting as pigmentation disorders. In this case report, we present a case of Alpers syndrome accompanied by hyperpigmentation and atrophy in skin folds.[ncbi.nlm.nih.gov]
  • In this case report, we present a case of Alpers syndrome accompanied by hyperpigmentation and atrophy in skin folds.[ncbi.nlm.nih.gov]
Pupillary Abnormality
  • The combination of pupillary abnormalities and TAs suggests that mitochondrial dysfunction may not explain the full extent of abnormalities in this case.[ncbi.nlm.nih.gov]
Calf Hypertrophy
  • In the muscular dystrophies, which tend to manifest in childhood or adolescence, dyspnea, cardiac abnormalities, contractures, scapular winging, calf hypertrophy, and skeletal deformities may be present in addition to slowly progressive weakness.[clevelandclinicmeded.com]
Neck Weakness
  • Weakness mainly involved proximal extremities, especially in the lower extremities, and bulbar and neck weakness were observed in some cases (13.7%). Creatine kinase was elevated in the majority of patients (97.9%).[ncbi.nlm.nih.gov]


Through a detailed patient history and a thorough physical examination, the physician plays a crucial role in raising clinical suspicion toward a mitochondrial myopathy. Several syndromes present with a distinct combination of demographic and clinical findings. For example, mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome should be suspected in individuals younger than 40 years of age who present with stroke-like episodes, seizures, migraine headaches, and has elevated lactate levels in blood [1] [4]. On the other hand, Kearns-Sayre syndrome (KSS) is the most likely diagnosis with an early onset (< 20 years of age) of extraocular muscle weakness, pigmentary retinopathy, and either cardiac conduction abnormalities, elevated proteins in the cerebrospinal fluid, or ataxia [1] [4]. For this reason, a meticulous laboratory and imaging assessment should follow clinical workup. A hormonal panel (thyroid stimulating hormone, cortisol, parathyroid hormone), glucose parameters (including hemoglobin A1c), serum electrolytes, and creatine kinase (CK) should be measured, while electrocardiography (ECG), electroencephalography (EEG), nerve conduction studies, magnetic resonance imaging (MRI) of the endocranium, a full ophthalmologic examination, and audiogram are recommended studies in order to evaluate the extent of organ damage and discriminate between different types [1]. To make a definite diagnosis of a mitochondrial myopathy, either a muscle biopsy and/or genetic studies are necessary [1] [3] [4] [5]. COX-deficient and succinate dehydrogenase (SDH)-positive muscle fibers are the hallmarks of a mitochondrial myopathy, whereas accumulated mitochondria in the subsarcolemmal area manifesting as either "ragged-blue fibers" or "ragged red fibers" (stained by SDH or Gomori trichrome stain, respectively), the pathognomonic features of mitochondrial myopathies [1].


  • Treatment Although there is no specific treatment for any of the mitochondrial myopathies, physical therapy may extend the range of movement of muscles and improve dexterity.[ninds.nih.gov]
  • Abstract Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO.[ncbi.nlm.nih.gov]
  • […] abnormal embryos left over from traditional fertility treatment.[news.bbc.co.uk]


  • Prognosis The prognosis for patients with mitochondrial myopathies varies greatly, depending largely on the type of disease and the degree of involvement of various organs.[ninds.nih.gov]
  • What is the prognosis for mitochondrial disease? The prognosis for patients with mitochondrial myopathies varies greatly, depending largely on the type of disease and the degree of involvement of various organs.[medicinenet.com]
  • The prognosis in our patients is relatively benign except one patient with the m.3302A G mutation. Copyright 2017 Elsevier B.V. All rights reserved.[ncbi.nlm.nih.gov]


  • Substance Publication type Case Reports MeSH terms Biopsy Chronic Disease DNA Mutational Analysis DNA, Mitochondrial/analysis DNA, Mitochondrial/genetics Gene Deletion Humans Inclusion Bodies/pathology Iris/pathology Iris/physiopathology Iris Diseases/etiology[ncbi.nlm.nih.gov]
  • Etiology A 656C-- T mutation in the nuclear pseudouridine synthase 1 gene ( PUS1 ), localised to 12q24.33, has recently been identified in some patients.[orpha.net]


  • Summary Epidemiology Less than 10 cases have been described so far. Etiology A 656C-- T mutation in the nuclear pseudouridine synthase 1 gene ( PUS1 ), localised to 12q24.33, has recently been identified in some patients.[orpha.net]
  • Molecular epidemiologic study of mitochondrial DNA mutations in patients with mitochondrial diseases in Taiwan. Pang CY, Huang CC, Yen MY, Wang EK, Kao KP, Chen SS, Wei YH.[thedoctorsdoctor.com]
  • View Article PubMed Google Scholar Chinnery PF, Johnson MA, Wardell TM, Singh-Kler R, Hayes C, Brown DT, Taylor RW, Bindoff LA, Turnbull DM: The epidemiology of pathogenic mitochondrial DNA mutations.[jmedicalcasereports.biomedcentral.com]
Sex distribution
Age distribution


  • These findings indicate that mitochondrial angiopathy plays an important role in the pathophysiology of MIMECK. L-arginine may be a potential therapeutic agent for this disorder. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • Although the exact pathophysiology of statin-induced myopathies is not fully understood, important mitochondrial cofactors arise from the cholesterol biosynthesis pathway, such as CoQ10.[michaelrucker.com]
  • […] inflammatory myopathies, including polymyositis, dermatomyositis, and inclusion body myositis, 2 3 and mitochondrial DNA abnormalities were recently described in patients with inclusion body myositis. 3 However, these changes are considered secondary and their pathophysiological[jnnp.bmj.com]
  • Non-genetic ways to damage mitochondria Cheney said that in the pathophysiology of CFIDS there are actually “lots of ways to screw up mitochondria without hitting its gene”.[prohealth.com]


  • To prevented further deterioration of the higher brain function, the early diagnosis and treatment of mitochondrial stroke-like episodes is important.[ncbi.nlm.nih.gov]
  • Natural Treatments for Mitochondrial Disease Treatments of mitochondrial issues are directed at the affected cells and preventing symptoms as well as associated conditions.[earthclinic.com]
  • […] further retinitis or optic atrophy • Ears – prevent further hearing loss • Systemic – growth - prevention of failure to thrive 13. • Brain • Seizure count • Age-appropriate neuropsychological testing • Headaches Diary • Stroke Count • Dozens of motor[slideshare.net]
  • The goals of this research are to increase scientific understanding of these disorders and to find ways to effectively treat, prevent, or potentially cure them. Information from the National Library of Medicine’s MedlinePlus Metabolic Disorders[ninds.nih.gov]



  1. Pfeffer G, Chinnery PF. Diagnosis and treatment of mitochondrial myopathies. Ann Med. 2013;45(1):4-16.
  2. Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet. 2008;83:254–260.
  3. Schoser BG, Pongratz D. Extraocular mitochondrial myopathies and their differential diagnoses. Strabismus. 2006;14(2):107-113.
  4. Berardo A, DiMauro S, Hirano M. A Diagnostic Algorithm for Metabolic Myopathies. Curr Neurol Neurosci Rep. 2010;10(2):118-126.
  5. Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008;1142:133–158.

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Last updated: 2019-07-11 20:50