Mitochondrial myopathy

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Mitochondrial myopathy
Other namesMitochondrial muscle disease; muscle mitochondrinopathy; muscle mitochondrial dysfunction
Animal mitochondrion diagram en (edit).svg
Simplified structure of a typical mitochondrion
Specialty Neuromuscular medicine

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. [1] Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced. [2]

Contents

Primary mitochondrial myopathies are inherited, while secondary mitochondrial myopathies may be inherited (e.g. Duchenne's muscular dystrophy) [3] or environmental (e.g. alcoholic myopathy [4] [5] ). When it is an inherited primary disease, it is one of the metabolic myopathies. [6] [4]

On biopsy, the muscle tissue of patients with these diseases usually demonstrate "ragged red" muscle fibers on Gomori trichrome staining. The ragged-red appearance is due to a buildup of abnormal mitochondria underneath the plasma membrane. [7] These ragged-red fibres may contain normal or abnormally increased accumulations of glycogen and neutral lipids, with histochemical staining showing abnormal respiratory chain involvement, such as decreased succinate dehydrogenase or cytochrome c oxidase. [8] Inheritance was believed to be maternal (non-Mendelian extranuclear). It is now known that certain nuclear DNA deletions can also cause mitochondrial myopathy such as the OPA1 gene deletion. [6]

Signs and symptoms

Proximal muscle weakness, exercise intolerance, lactic acidosis, high serum lactate/pyruvate ratio, normal to elevated serum CK, dyspnea, exaggerated cardiorespiratory response to exercise are common symptoms. It may be isolated to the muscle (pure myopathy) or may be systemic including not only myopathy, but also eye abnormalities, peripheral neuropathy, and neurological abnormalities. Muscle biopsy typically shows ragged-red fibres, histochemical staining shows abnormality of respiratory chain or decreased cytochrome c oxidase (COX). [9] [10]

The five most common are MELAS, MERF, KSS, CPEO, and MNGIE which are listed below: [9]

Cause

Many mitochondrial myopathies have mitochondrial inheritance Mitochondrial inheritance.svg
Many mitochondrial myopathies have mitochondrial inheritance

Mitochondrial myopathy literally means mitochondrial muscle disease, muscle disease caused by mitochondrial dysfunction. The mitochondrion is the primary producer of energy in nearly all cells throughout the body. The exception is mature erythrocytes (red blood cells), so that they do not use up the oxygen that they carry. In the eye, the lens and outer segment of the retina contain almost no mitochondria. Muscle cells have many mitochondria, particularly type I muscle fibres, and if the mitochondria have problems by which they do not produce enough energy for the cell to function, problems occur. [11]

The cause may be genetic, with many having mitochondrial inheritance (involving the mitochondrial DNA which is only passed on from the mother), although nuclear DNA mutations with Mendelian inheritance that are either autosomal dominant, recessive, or X-linked recessive also exist. A nuclear DNA example is a mutation within the POLG (polymerase gamma) gene, which causes mitochondrial DNA (mtDNA) to become damaged and lose function.

Disease list

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by adding missing items with reliable sources.
Name

(alternate names)

Gene(s) Inheritance pattern

(MT, AR, AD, X-Linked)

 OMIM #

(GD: gene description, PS: phenotypic series)

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS)

(Juvenile myopathy, encephalopathy, lactic acidosis and stroke)

 MT-TL1, MT-TQ, MT-TH, MT-TK, MT-TC, MT-TS1, MT-ND1, MT-ND5, MT-ND6, MT-TS2 MT540000 [12]
Myoclonic epilepsy and ragged-red fibers (MERRF) MT-TK, MT-TL1, MT-TH, MT-TS1, MT-TS2, MT-TF MT545000 [13]
Kearns–Sayre syndrome (KSS)

(Ophthalmoplegia, pigmentary degeneration of retina, and cardiomyopathy; oculocraniosomatic syndrome; ophthalmoplegia-plus syndrome; mitochondrial cytopathy, ophthalmoplegia, progressive external, with ragged-red fibers; chronic progressive external ophthalmoplegia with myopathy; CPEO with myopathy; CPEO with ragged-red fibers)

 MT-TL1 MT530000 [14]
Chronic progressive external ophthalmoplegia (CPEO)

(Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive/dominant)

 POLG, SLC25A4, RNASEH1, TWNK, TK2, POLG2, DGUOK, TOP3A, RRM2B AR/ADPS157640 [15]
Mitochondrial DNA depletion syndrome (MNGIE type)

(Mitochondrial neurogastrointestinal encephalopathy (MNGIE); myoneurogastrointestinal encephalopathy syndrome; polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudoobstruction; POLIP syndrome)

 TYMP, RRM2B, POLG, LIG3 AR603041;

612075;

613662;

619780 [16]

Mitochondrial DNA depletion syndrome

(Alpers type, cardiomyopathic type, encephalomyopathic type, hepatocerebral type, and myopathic type)

MGME1, SLC25A10, TK2, POLG, SLC25A21, SUCLA2, TWNK, TFAM, AGK, MRM2, SLC25A4, OPA1, SUCLG1 AR/ADPS603041 [16]
Mitochondrial myopathy, infantile, transient (MMIT)

(Mitochondrial myopathy, infantile, transient, due to respiratory chain deficiency; COX deficiency myopathy, infantile, transient; respiratory chain deficiency, infantile, transient)

 MT-TE MT500009 [17]
Mitochondrial myopathy, lethal, infantile (LIMM)

(Lethal infantile mitochondrial myopathy)

 MT-TT MT551000 [18]
Hereditary myopathy with lactic acidosis (HML)

(Myopathy with exercise intolerance, Swedish type; myopathy with deficiency of succinate dehydrogenase and aconitase; myoglobinuria due to abnormal glycolysis; Larsson–Linderholm syndrome; Linderholm myopathy)

 ISCU AR/AD [19] 255125 [20]
Mitochondrial myopathy with diabetes

(Mitochondrial myopathy, lipid type)

 MT-TE MT500002 [21]
Maternally inherited diabetes and deafness (MIDD)

(Diabetes and deafness (DAD); Ballinger–Wallace syndrome; Noninsulin-dependent diabetes mellitus with deafness, maternally inherited)

 MT-TL1, MT-TE, MT-TK MT520000 [22]
Myopathy, mitochondrial progressive, with congenital cataract and developmental delay (MPMCD)

(Myopathy with cataract and combined respiratory chain deficiency; mitochondrial complex deficiency, combined)

 GFER AR613076 [23]
Myopathy, lactic acidosis, and sideroblastic anemia (MLASA)

(Mitochondrial myopathy and sideroblastic anemia)

 PUS1, YARS2, MT-ATP6 AR/MT600462

613561 [24]

GD: 516060 [25]

Myopathy, isolated mitochondrial, autosomal dominant (IMMD) CHCHD10 AD616209 [26]
Myopathy, mitochondrial, and ataxia (MMYAT) MSTO1 AR/AD617675 [27]
Mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy (MEOAL) FDX2 AR251900 [28]
Mitochondrial myopathy with lactic acidosis (MMLA) PNPLA8 AR251950 [29]
Mitochondrial myopathy with a defect in mitochondrial-protein transportUnknownAR251945 [30]
Myotonic dystrophy-like myopathy;

Mitochondrial myopathy

 MT-TA MTGD: 590000 [31]
Mitochondrial myopathy, isolated MT-TD MTGD: 590015 [32]
Myopathy, mitochondrial MT-TW MTGD: 590095 [33]
Coenzyme Q10 deficiency, primary (COQ10D)

(CoQ10 deficiency, primary; ubiquinone deficiency; Coenzyme Q deficiency; CoQ deficiency)

 COQ2, PDSS1, PDSS2, ADCK3, COQ9, COQ4, COQ7, COQ5 ARPS607426 [34]
Mitochondrial complex I deficiency, nuclear type (MC1DN)

(NADH:Q(1) oxidoreductase deficiency; NADH-coenzyme Q reductase deficiency; mitochondrial NADH dehydrogenase component of complex I, deficiency of)

 NDUFS2, NDUFB3, NDUFS1, NDUFA10, NDUFAF3, TIMMDC1, ACAD9, NDUFS6, NDUFS4, NDUFAF2, NDUFA2, NDUFAF4, DNAJC30, NDUFAF6, NDUFB9, NDUFA8, NDUFB8, NDUFS3, NDUFV1, NDUFS8, NDUFC2, TMEM126B, FOXRED1, NDUFA9, NDUFA12, NUBPL, NDUFAF1, MTFMT, NDUFB10, NDUFAF8, NDUFV2, NDUFS7, NDUFA11, NDUFB7, NDUFA13, NDUFAF5, NDUFA6, NDUFB11, NDUFA1 AR/XL/XLRPS252010 [35]
Mitochondrial complex II deficiency, nuclear type (MC2DN)

(Succinate CoQ reductase deficiency; succinate dehydrogenase deficiency)

 SDHA, SDHAF1, SDHD, SDHB ARPS252011 [36]
cytochrome b of complex III (MTCYB);

Exercise intolerance; multisystem disorder; cardiomyopathy, infantile histiocytoid; exercise intolerance, cardiomyopathy, and septooptic dysplasia; parkinsonism/MELAS overlap syndrome

MT-CYB MTGD: 516020 [37]
Mitochondrial complex III deficiency, nuclear type (MC3DN) BCS1L, TTC19, UQCRQ, UQCRC2, CYC1, UQCC2, LYRM7, UQCC3, UQCRFS1 ARPS124000 [38]
Mitochondrial complex IV deficiency, nuclear type (MC4DN)

(mitochondrial complex IV deficiency; cytochrome c oxidase deficiency; COX deficiency)

 SURF1, SCO2, COX10, SCO1, LRPPRC, COX15, COX6B1, TACO1, COX14, COX20, PET100, COA6, COA3, COX8A, COX4I1, APOPT1, COX6A2, PET117, COX5A, COXFA4, COX16, COX11ARPS220110 [39]
Mitochondrial complex V (ATP synthase) deficiency, nuclear type (MC5DN) ATPAF2, TMEM70, ATP5E, ATP5F1A, ATP5F1D, ATP5MD, ATP5PO AR/ADPS604273 [40]
Muscular dystrophy, limb-girdle, type 1H

(As of 2017 was excluded from LGMD for showing histochemical evidence of being a mitochondrial myopathy, but not yet assigned new nomenclature) [41] [42]

Chromosome 3 (3p23-p25), unknown geneAD613530 [43]

Diagnosis

Very high magnification micrograph showing ragged red fibres in a mitochondrial myopathy. Gomoi trichrome stain. Ragged red fibres - gtc - very high mag.jpg
Very high magnification micrograph showing ragged red fibres in a mitochondrial myopathy. Gömöi trichrome stain.

Muscle biopsy: usually ragged red fibres in Gömöri trichrome stain, normal or excessive glycogen or lipid accumulation within these ragged red fibres, histochemical staining showing impairment of respiratory chain such as COX-negative fibres. [6] [8] Some mitochondrial myopathies are limited to disease expression only in skeletal muscle, with fibroblasts (from skin biopsy) appearing normal. [44] [19]

Blood tests: lactate/pyruvate ratio may be elevated or normal, creatine kinase (CK) may be elevated or normal. [6] [2] Electrolyte panel, anion gap, glucose, vitamin D, TSH, anti-HMGCR and AChR autoantibodies to rule-out pseudometabolic myopathies. [6] [2]

Exercise stress test: exaggerated cardiorespiratory response to exercise (inappropriate rapid heart rate response to exercise with breathlessness [ tachycardia and dyspnea]). [10]

DNA tests: whole exome sequencing (WES) neuromuscular panels (that only test exons), or whole genome sequencing (WGS) for more complex cases (that test exons, introns, and mitochondrial DNA). Introns were initially thought to be "junk DNA," however, some introns regulate the expression of exons. [45] [46] For example, in the mitochondrial myopathy of hereditary myopathy with lactic acidosis (HML), the most common pathogenic mutation is the intronic IVS5+382 G>C (rs767000507). [19]

There are two groups of DNA that affect the mitochondria: mitochondrial genome (mtDNA) and nuclear DNA. [6] For mitochondrial myopathies that involve a single mtDNA deletion, it would only be found on muscle-derived mtDNA, making a biopsy of affected muscle necessary for DNA analysis rather than saliva or blood. [6] [8] Even among siblings with the same inherited mutation, different muscle groups were affected, with unaffected tissues having near normal levels of mtDNA. [47] [48]

EMG: may be normal, myopathic, or rarely neurogenic. [6]

The symptoms of exercise intolerance, abnormal muscle fatigue, myalgia (muscle pain), arrhythmia, possible fixed proximal muscle weakness, lipid deposits, possible episodes of rhabdomyolysis, with symptoms becoming evident or worsening while fasting, during a fever, during low-intensity aerobic activity or after prolonged activity–all these overlap with the symptoms of another metabolic myopathy, that of fatty acid metabolism disorders. [6]

DNA testing is helpful for determining between the similar presenting, but different in bioenergetic system origin, metabolic myopathies. When DNA testing is inconclusive, a muscle biopsy is necessary. [2] [6] [8]

Differential diagnoses

Diseases that mimic the symptoms of mitochondrial myopathy include electrolyte imbalance, myasthenia gravis, thyroid abnormalities, vitamin D deficiency, immune-mediated necrotizing myopathy, diabetes-related pseudohypoxia, and fatty acid metabolism disorders. [6] [2] Hypoxia due to ischemia (insufficient blood flow) also impairs oxidative phosphorylation, which can be seen in intermittent claudication, chronic venous insufficiency, and popliteal artery entrapment syndrome. If symptoms of muscle fatigue improve after approximately 10 minutes of low-moderate intensity aerobic exercise, or after approximately 10 minutes of rest following aerobic exercise, this would be indicative of the second wind phenomenon seen in select muscle glycogenoses. [2]

Ragged red fibres (a mitochondrial abnormality) can be found in a number of myopathies other than the inherited primary mitochondrial myopathies. [49] These include axonal Charcot–Marie–Tooth disease types 2CC & 2EE, congenital myasthenic syndrome types 12 & 14, congenital myopathy types 10B & 22A, and MYH7-related myopathies such as Laing distal myopathy and myosin storage myopathy. [49]

Secondary mitochondrial myopathy can be caused by natural aging, [50] [51] inflammatory myopathies, [50] and chronic alcohol use disorder. [4] [5] It can also be due to certain drugs such statins, bupivacaine, antiepileptic drugs (phenytoin, valproic acid, and lamotrigine), and nucleoside reverse transcriptase inhibitors (antiviral drugs) such as zidovudine and clevudine. [52]

Some metabolic myopathies affect multiple bioenergetic pathways, for instance multiple acyl-CoA dehydrogenase deficiency (MADD), formerly known as glutaric acidemia type II (GA-II). The ETF genes involved in MADD impairs beta oxidation (fatty acid metabolism), impairs amino acid catabolism (protein metabolism), and simultaneously impairs the respiratory chain by not transferring electrons from reduced FAD+/FADH2. The impaired protein metabolism leads to a buildup of glutaric acid and other acids. Fatty acid metabolism is further impaired as carnitine is used to detoxify the buildup of glutaric acid, causing secondary carnitine deficiency. [53] [54] Although MADD affects multiple bioenergetic pathways, it is classified as a fatty acid metabolism disorder as that is the bioenergetic pathway that is affected the most by the deficiency. However, it is important to note as a differential diagnosis as not only do the symptoms overlap with mitochondrial myopathies, but also muscle biopsies of some individuals with MADD show COX-negative fibres, respiratory chain impairment, and deficiency of coenzyme Q10. [55] [56] Some forms of MADD respond well to riboflavin, known as riboflavin-responsive MADD (RR-MADD). [6]

Riboflavin-responsive exercise intolerance (RREI), a fatty acid metabolism disorder involving the SLC25A32 gene, has symptoms similar to MADD, with muscle biopsy showing ragged red fibres and lipid deposits (mainly in type I fibres), small type II fibres, and impaired FAD-dependent mitochondrial respiratory chain. [57]

Pompe disease (glycogen storage disease type II), another type of metabolic myopathy, has secondary mitochondrial dysfunction present in both the earlier onset forms (infantile and juvenile) and the late-onset form in adults. [58]

Myopathies involving the DMD gene, such as Duchenne and Becker muscular dystrophy, have secondary mitochondrial dysfunction impairing oxidative phosphorylation. [3] [59] The mechanisms leading to this mitochondrial dysfunction are many and it has yet to be elucidated which mitochondrial changes are directly due to the disease and which are compensatory. [3] Three unrelated young boys, with a mutation in the DMD gene, exhibited a pseudometabolic presentation with symptoms of exercise intolerance manifesting as exercise-induced myalgia, muscle stiffness, myoglobinuria and rhabdomyolysis. [60]

A few Limb–girdle muscular dystrophies are known to have secondary mitochondrial dysfunction, including: LGMDR1 calpain3-related (formerly LGMD 2A), LGMDR2 dysferlin-related (LGMD 2B), LGMDR3 α-sarcoglycan-related (LGMD 2D), LGMDR5 γ-sarcoglycan-related (LGMD 2C), and LGMDR6 δ-sarcoglycan-related (LGMD 2F). [59] [61] As well as Myofibrillar myopathy 8 (MFM8) PYROXD1-related, which has an adult-onset, slowly progressive, Limb–girdle phenotype. [59] [62]

Treatment

Although no cure currently exists, there is hope in treatment for this class of hereditary diseases as trials continue.

Aerobic training may improve oxidative capacity by the skeletal muscles becoming aerobically conditioned. Deoxynucleoside monophosphates and deoxynucleotide taken orally, may help in TK2 deficiency (Mitochondrial DNA depletion syndrome 2 myopathic type). [6]

Avoiding physically stressful situations that deplete glycogen reserves, such as fasting and endurance exercise (which rely predominantly on oxidative phosphorylation), may help. A high-carb/low-fat/low-protein diet may help. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Adenosine monophosphate deaminase deficiency type 1</span> Medical condition

Adenosine monophosphate deaminase deficiency type 1 or AMPD1, is a human metabolic disorder in which the body consistently lacks the enzyme AMP deaminase, in sufficient quantities. This may result in exercise intolerance, muscle pain and muscle cramping. The disease was formerly known as myoadenylate deaminase deficiency (MADD).

<span class="mw-page-title-main">Glycogen storage disease</span> Medical condition

A glycogen storage disease is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.

<span class="mw-page-title-main">Lactic acidosis</span> Metabolic medical condition

Lactic acidosis is a medical condition characterized by a build-up of lactate in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism.

Muscle fatigue is when muscles that were initially generating a normal amount of force, then experience a declining ability to generate force. It can be a result of vigorous exercise, but abnormal fatigue may be caused by barriers to or interference with the different stages of muscle contraction. There are two main causes of muscle fatigue: the limitations of a nerve’s ability to generate a sustained signal ; and the reduced ability of the muscle fiber to contract.

<span class="mw-page-title-main">Exercise intolerance</span> Medical condition

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders.

Glutaric acidemia type 2 is an autosomal recessive metabolic disorder that is characterised by defects in the ability of the body to use proteins and fats for energy. Incompletely processed proteins and fats can build up, leading to a dangerous chemical imbalance called acidosis. It is a metabolic myopathy, categorized under fatty acid metabolism disorder as that is the bioenergetic system that it affects the most. It also affects choline metabolism.

<span class="mw-page-title-main">MELAS syndrome</span> Medical condition

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include MIDD, MERRF syndrome, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984. A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent. The most common MELAS mutation is mitochondrial mutation, mtDNA, referred to as m.3243A>G.

Pyruvate dehydrogenase deficiency is a rare neurodegenerative disorder associated with abnormal mitochondrial metabolism. PDCD is a genetic disease resulting from mutations in one of the components of the pyruvate dehydrogenase complex (PDC). The PDC is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria. The disorder shows heterogeneous characteristics in both clinical presentation and biochemical abnormality.

Mitochondrially encoded tRNA leucine 1 (UUA/G) also known as MT-TL1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL1 gene.

<span class="mw-page-title-main">ISCU</span> Mammalian protein found in Homo sapiens

Iron-sulfur cluster assembly enzyme ISCU, mitochondrial is a protein that in humans is encoded by the ISCU gene. It encodes an iron-sulfur (Fe-S) cluster scaffold protein involved in [2Fe-2S] and [4Fe-4S] cluster synthesis and maturation. A deficiency of ISCU is associated with a mitochondrial myopathy with lifelong exercise intolerance where only minor exertion causes tachycardia, shortness of breath, muscle weakness and myalgia.

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

<span class="mw-page-title-main">Metabolic myopathy</span> Type of myopathies

Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects that interfere with muscle's ability to create energy, causing a low ATP reservoir within the muscle cell.

Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene. MT-TE is a small 69 nucleotide RNA that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation.

Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene.

Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.

Mitochondrially encoded tRNA leucine 2 (CUN) also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene.

<span class="mw-page-title-main">Purine nucleotide cycle</span>

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.

<span class="mw-page-title-main">Sengers syndrome</span> Medical condition

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. Biallelic pathogenic mutations in the AGK gene, which encodes the acylglycerol kinase enzyme, cause Sengers syndrome. In addition, heart disease and muscle disease are prevalent, meaning that life expectancy is short for many patients.

<span class="mw-page-title-main">Pseudoathletic appearance</span> Medical sign

Pseudoathletic appearance is a medical sign meaning to have the false appearance of a well-trained athlete due to pathologic causes instead of true athleticism. It is also referred to as a Herculean or bodybuilder-like appearance. It may be the result of muscle inflammation, muscle hyperplasia, muscle hypertrophy, muscle pseudohypertrophy, or symmetrical subcutaneous deposits of fat or other tissue.

References

  1. ↑ "Mitochondrial Myopathy Information Page | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2017-02-28.
  2. 1 2 3 4 5 6 Bhai S (September 2021). "Neuromuscular Notes: Diagnosing Metabolic Myopathies". Practical Neurology.
  3. 1 2 3 Heydemann A (June 2018). "Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy-Implications for Therapies". Nutrients. 10 (6): 796. doi: 10.3390/nu10060796 . PMC   6024668 . PMID   29925809.
  4. 1 2 3 Simon L, Jolley SE, Molina PE (2017). "Alcoholic Myopathy: Pathophysiologic Mechanisms and Clinical Implications". Alcohol Research. 38 (2): 207–217. PMC   5513686 . PMID   28988574.
  5. 1 2 Song BJ, Akbar M, Abdelmegeed MA, Byun K, Lee B, Yoon SK, Hardwick JP (2014-01-01). "Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications". Redox Biology. 3: 109–123. doi: 10.1016/j.redox.2014.10.004 . PMC   4297931 . PMID   25465468. S2CID   17113550.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Urtizberea JA, Severa G, Malfatti E (April 2023). "Metabolic Myopathies in the Era of Next-Generation Sequencing". Genes. 14 (5): 954. doi: 10.3390/genes14050954 . PMC   10217901 . PMID   37239314.
  7. ↑ "Ragged-red muscle fibers - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-01-05.
  8. 1 2 3 4 Sarnat, Harvey B.; Marín-García, José (May 2005). "Pathology of Mitochondrial Encephalomyopathies". Canadian Journal of Neurological Sciences. 32 (2): 152–166. doi: 10.1017/S0317167100003929 . ISSN   0317-1671. PMID   16018150. S2CID   1922603.
  9. 1 2 Tobon A (December 2013). "Metabolic myopathies". Continuum. 19 (6 Muscle Disease): 1571–1597. doi:10.1212/01.CON.0000440660.41675.06. PMC   10563931 . PMID   24305448. S2CID   11050341.
  10. 1 2 Noury JB, Zagnoli F, Petit F, Marcorelles P, Rannou F (May 2020). "Exercise efficiency impairment in metabolic myopathies". Scientific Reports. 10 (1): 8765. Bibcode:2020NatSR..10.8765N. doi:10.1038/s41598-020-65770-y. PMC   7260200 . PMID   32472082.
  11. ↑ "Nutrient Metabolism, Human | Learn Science at Scitable". www.nature.com. Retrieved 2024-04-05.
  12. ↑ "#540000 - MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES; MELAS". www.omim.org. Retrieved 2023-11-24.
  13. ↑ "#545000 - MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS; MERRF". www.omim.org. Retrieved 2023-11-24.
  14. ↑ "#530000 - KEARNS-SAYRE SYNDROME; KSS". www.omim.org. Retrieved 2023-11-24.
  15. ↑ "Phenotypic Series - PS157640 - CPEO - OMIM". www.omim.org. Retrieved 2023-11-24.
  16. 1 2 "Phenotypic Series - PS603041 - Mitochondrial DNA depletion syndrome - OMIM". www.omim.org. Retrieved 2023-11-24.
  17. ↑ "#500009 - MITOCHONDRIAL MYOPATHY, INFANTILE, TRANSIENT; MMIT". www.omim.org. Retrieved 2023-11-24.
  18. ↑ "#551000 - MITOCHONDRIAL MYOPATHY, LETHAL, INFANTILE; LIMM". www.omim.org. Retrieved 2023-11-30.
  19. 1 2 3 Legati, Andrea; Reyes, Aurelio; Ceccatelli Berti, Camilla; Stehling, Oliver; Marchet, Silvia; Lamperti, Costanza; Ferrari, Alberto; Robinson, Alan J.; Mühlenhoff, Ulrich; Lill, Roland; Zeviani, Massimo; Goffrini, Paola; Ghezzi, Daniele (December 2017). "A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy". Journal of Medical Genetics. 54 (12): 815–824. doi:10.1136/jmedgenet-2017-104822. ISSN   1468-6244. PMC   5740555 . PMID   29079705.
  20. ↑ "#255125 - MYOPATHY WITH LACTIC ACIDOSIS, HEREDITARY; HML". www.omim.org. Retrieved 2023-11-24.
  21. ↑ "#500002 - MITOCHONDRIAL MYOPATHY WITH DIABETES". www.omim.org. Retrieved 2023-11-24.
  22. ↑ "DIABETES AND DEAFNESS, MATERNALLY INHERITED; MIDD - OMIM". www.omim.org. Retrieved 2024-03-02.
  23. ↑ "#613076 - MYOPATHY, MITOCHONDRIAL PROGRESSIVE, WITH CONGENITAL CATARACT AND DEVELOPMENTAL DELAY; MPMCD". www.omim.org. Retrieved 2023-11-24.
  24. ↑ "Phenotypic Series - PS600462 - Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) - OMIM". www.omim.org. Retrieved 2023-11-30.
  25. ↑ "Allelic Variants - 516060 - MT-ATP6 - OMIM". www.omim.org. Retrieved 2023-11-30.
  26. ↑ "616209 - MYOPATHY, ISOLATED MITOCHONDRIAL, AUTOSOMAL DOMINANT; IMMD". www.omim.org. Retrieved 2023-11-30.
  27. ↑ "#617675 - MYOPATHY, MITOCHONDRIAL, AND ATAXIA; MMYAT". www.omim.org. Retrieved 2023-11-30.
  28. ↑ "#251900 - MITOCHONDRIAL MYOPATHY, EPISODIC, WITH OR WITHOUT OPTIC ATROPHY AND REVERSIBLE LEUKOENCEPHALOPATHY; MEOAL". www.omim.org. Retrieved 2023-11-30.
  29. ↑ "#251950 - MITOCHONDRIAL MYOPATHY WITH LACTIC ACIDOSIS; MMLA". www.omim.org. Retrieved 2023-11-30.
  30. ↑ "251945 - MITOCHONDRIAL MYOPATHY WITH A DEFECT IN MITOCHONDRIAL-PROTEIN TRANSPORT". www.omim.org. Retrieved 2023-11-30.
  31. ↑ "*590000 - TRANSFER RNA, MITOCHONDRIAL, ALANINE; MTTA". www.omim.org. Retrieved 2023-11-30.
  32. ↑ "*590015 - TRANSFER RNA, MITOCHONDRIAL, ASPARTIC ACID; MT-TD". www.omim.org. Retrieved 2023-11-30.
  33. ↑ "Allelic Variants - 590095 - RANSFER RNA, MITOCHONDRIAL, TRYPTOPHAN; MT-TW - OMIM". www.omim.org. Retrieved 2023-11-30.
  34. ↑ "Phenotypic Series - PS607426 - Coenzyme Q10 deficiency - OMIM". omim.org. Retrieved 2023-11-30.
  35. ↑ "Phenotypic Series - PS252010 - Mitochondrial Complex I deficiency, nuclear type - OMIM". www.omim.org. Retrieved 2023-11-30.
  36. ↑ "Phenotypic Series - PS252011 - mitochondrial complex II - OMIM". www.omim.org. Retrieved 2023-11-30.
  37. ↑ "Allelic Variants - 516020 - cytochrome b of complex III - OMIM". www.omim.org. Retrieved 2023-11-30.
  38. ↑ "Phenotypic Series - PS124000 - Mitochondrial complex III deficiency, nuclear type - OMIM". www.omim.org. Retrieved 2023-12-01.
  39. ↑ "Phenotypic Series - PS220110 - Mitochondrial complex IV deficiency - OMIM". www.omim.org. Retrieved 2023-11-30.
  40. ↑ "Phenotypic Series - PS604273 - Mitochondrial complex V deficiency - OMIM". www.omim.org. Retrieved 2023-12-01.
  41. ↑ Straub V, Murphy A, Udd B (August 2018). "229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017". Neuromuscular Disorders. 28 (8): 702–710. doi: 10.1016/j.nmd.2018.05.007 . PMID   30055862. S2CID   51865029.
  42. ↑ Bisceglia L, Zoccolella S, Torraco A, Piemontese MR, Dell'Aglio R, Amati A, et al. (June 2010). "A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H". European Journal of Human Genetics. 18 (6): 636–641. doi:10.1038/ejhg.2009.235. PMC   2987336 . PMID   20068593.
  43. ↑ "613530 - MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1H; LGMD1H". www.omim.org. Retrieved 2023-11-30.
  44. ↑ Sanaker, Petter S.; Toompuu, Marina; Hogan, Vanessa E.; He, Langping; Tzoulis, Charalampos; Chrzanowska-Lightowlers, Zofia M. A.; Taylor, Robert W.; Bindoff, Laurence A. (2010-06-01). "Differences in RNA processing underlie the tissue specific phenotype of ISCU myopathy". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1802 (6): 539–544. doi:10.1016/j.bbadis.2010.02.010. ISSN   0925-4439.
  45. ↑ Shaul, Orit (2017-10-01). "How introns enhance gene expression". The International Journal of Biochemistry & Cell Biology. Splicing. 91: 145–155. doi:10.1016/j.biocel.2017.06.016. ISSN   1357-2725.
  46. ↑ "What is noncoding DNA?: MedlinePlus Genetics". medlineplus.gov. Retrieved 2024-04-11.
  47. ↑ Moraes, C. T.; Shanske, S.; Tritschler, H. J.; Aprille, J. R.; Andreetta, F.; Bonilla, E.; Schon, E. A.; DiMauro, S. (March 1991). "mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases". American Journal of Human Genetics. 48 (3): 492–501. ISSN   0002-9297. PMC   1682992 . PMID   1998336.
  48. ↑ "#609560 - MITOCHONDRIAL DNA DEPLETION SYNDROME 2 (MYOPATHIC TYPE); MTDPS2". www.omim.org. Retrieved 2023-12-06.
  49. 1 2 "Ragged-red muscle fibers (Concept Id: C3275417) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-06.
  50. 1 2 Rifai Z, Welle S, Kamp C, Thornton CA (January 1995). "Ragged red fibers in normal aging and inflammatory myopathy". Annals of Neurology. 37 (1): 24–29. doi:10.1002/ana.410370107. PMID   7818253. S2CID   23909958.
  51. ↑ Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, et al. (December 2013). "Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging". Cell. 155 (7): 1624–1638. doi:10.1016/j.cell.2013.11.037. PMC   4076149 . PMID   24360282.
  52. ↑ Kim JM (November 2017). "Myopathy, Drugs, and Mitochondria". Journal of Korean Medical Science. 32 (11): 1732–1733. doi:10.3346/jkms.2017.32.11.1732. PMC   5639049 . PMID   28960021.
  53. ↑ Coulter DL (2014-01-01). "Carnitine Deficiency". In Aminoff MJ, Daroff RB (eds.). Encyclopedia of the Neurological Sciences (Second ed.). Oxford: Academic Press. pp. 597–599. doi:10.1016/B978-0-12-385157-4.00079-8. ISBN   978-0-12-385158-1 . Retrieved 2023-11-30.
  54. ↑ Li Q, Yang C, Feng L, Zhao Y, Su Y, Liu H, et al. (2021). "Glutaric Acidemia, Pathogenesis and Nutritional Therapy". Frontiers in Nutrition. 8: 704984. doi: 10.3389/fnut.2021.704984 . PMC   8714794 . PMID   34977106.
  55. ↑ Béhin A, Acquaviva-Bourdain C, Souvannanorath S, Streichenberger N, Attarian S, Bassez G, et al. (March 2016). "Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease". Revue Neurologique. 172 (3): 231–241. doi:10.1016/j.neurol.2015.11.008. PMID   27038534.
  56. ↑ Henriques BJ, Katrine Jentoft Olsen R, Gomes CM, Bross P (April 2021). "Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease". Gene. 776: 145407. doi:10.1016/j.gene.2021.145407. PMC   7949704 . PMID   33450351.
  57. ↑ "#616839 - EXERCISE INTOLERANCE, RIBOFLAVIN-RESPONSIVE; RREI". www.omim.org. Retrieved 2023-11-24.
  58. ↑ Schoser, B. G. H.; Müller-Höcker, J.; Horvath, R.; Gempel, K.; Pongratz, D.; Lochmüller, H.; Müller-Felber, W. (October 2007). "Adult-onset glycogen storage disease type 2: clinico-pathological phenotype revisited". Neuropathology and Applied Neurobiology. 33 (5): 544–559. doi:10.1111/j.1365-2990.2007.00839.x. ISSN   0305-1846. PMID   17573812. S2CID   25822083.
  59. 1 2 3 Saha, Madhurima; Reddy, Hemakumar M.; Salih, Mustafa A.; Estrella, Elicia; Jones, Michael D.; Mitsuhashi, Satomi; Cho, Kyung-Ah; Suzuki-Hatano, Silveli; Rizzo, Skylar A.; Hamad, Muddathir H.; Mukhtar, Maowia M.; Hamed, Ahlam A.; Elseed, Maha A.; Lek, Monkol; Valkanas, Elise (2018-11-01). "Impact of PYROXD1 deficiency on cellular respiration and correlations with genetic analyses of limb-girdle muscular dystrophy in Saudi Arabia and Sudan". Physiological Genomics. 50 (11): 929–939. doi:10.1152/physiolgenomics.00036.2018. ISSN   1531-2267. PMC   6293114 . PMID   30345904.
  60. ↑ Veerapandiyan A, Shashi V, Jiang YH, Gallentine WB, Schoch K, Smith EC (December 2010). "Pseudometabolic presentation of dystrophinopathy due to a missense mutation". Muscle & Nerve. 42 (6): 975–979. doi:10.1002/mus.21823. PMC   5506871 . PMID   21104870.
  61. ↑ Barton, Elisabeth R.; Pacak, Christina A.; Stoppel, Whitney L.; Kang, Peter B. (2020-07-29). "The ties that bind: functional clusters in limb-girdle muscular dystrophy". Skeletal Muscle. 10 (1): 22. doi: 10.1186/s13395-020-00240-7 . ISSN   2044-5040. PMC   7389686 . PMID   32727611.
  62. ↑ Sainio, Markus T.; Välipakka, Salla; Rinaldi, Bruno; Lapatto, Helena; Paetau, Anders; Ojanen, Simo; Brilhante, Virginia; Jokela, Manu; Huovinen, Sanna; Auranen, Mari; Palmio, Johanna; Friant, Sylvie; Ylikallio, Emil; Udd, Bjarne; Tyynismaa, Henna (February 2019). "Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy". Journal of Neurology. 266 (2): 353–360. doi:10.1007/s00415-018-9137-8. ISSN   1432-1459. PMC   6373352 . PMID   30515627.
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