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|Simplified structure of a typical mitochondrion|
Mitochondrial myopathies are types of myopathies associated with mitochondrial disease.On biopsy, the muscle tissue of patients with these diseases usually demonstrate "ragged red" muscle fibers. These ragged-red fibers contain mild accumulations of glycogen and neutral lipids, and may show an increased reactivity for succinate dehydrogenase and a decreased reactivity for cytochrome c oxidase. 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. There are several subcategories of mitochondrial myopathies.
Signs and symptoms include (for each of the following causes):
Zidovudine, an HIV medication can cause red ragged fiber myopathy.
Muscle biopsy: ragged red fibers in Gömöri trichrome stain.
Although no cure currently exists, there is hope in treatment for this class of hereditary diseases with the use of an embryonic mitochondrial transplant.
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.
Kearns–Sayre syndrome (KSS), Oculocraniosomatic disorder or Oculocranionsomatic neuromuscular disorder with ragged red fibers, is a mitochondrial myopathy with a typical onset before 20 years of age. KSS is a more severe syndromic variant of chronic progressive external ophthalmoplegia, a syndrome that is characterized by isolated involvement of the muscles controlling movement of the eyelid and eye. This results in ptosis and ophthalmoplegia respectively. KSS involves a combination of the already described CPEO as well as pigmentary retinopathy in both eyes and cardiac conduction abnormalities. Other symptoms may include cerebellar ataxia, proximal muscle weakness, deafness, diabetes mellitus, growth hormone deficiency, hypoparathyroidism, and other endocrinopathies. In both of these diseases, muscle involvement may begin unilaterally but always develops into a bilateral deficit, and the course is progressive. This discussion is limited specifically to the more severe and systemically involved variant.
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include 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.
Myoclonic epilepsy refers to a family of epilepsies that present with myoclonus. When myoclonic jerks are occasionally associated with abnormal brain wave activity, it can be categorized as myoclonic seizure. If the abnormal brain wave activity is persistent and results from ongoing seizures, then a diagnosis of myoclonic epilepsy may be considered.
MERRF syndrome is a mitochondrial disease. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. MERRF syndrome affects different parts of the body, particularly the muscles and nervous system. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. The causes of MERRF syndrome are difficult to determine, but because it is a mitochondrial disorder, it can be caused by the mutation of nuclear DNA or mitochondrial DNA. The classification of this disease varies from patient to patient, since many individuals do not fall into one specific disease category. The primary features displayed on a person with MERRF include myoclonus, seizures, cerebellar ataxia, myopathy, and ragged red fibers (RRF) on muscle biopsy, leading to the disease's name. Secondary features include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity, or multiple lipomata. Mitochondrial disorders, including MERRFS, may present at any age.
Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:
Progressive myoclonus epilepsy (PME) is a rare epilepsy syndrome caused by a variety of genetic disorders. The syndrome includes myoclonic seizures and tonic-clonic seizures together with progressive neurological decline.
Chronic progressive external ophthalmoplegia (CPEO), is a type of eye disorder characterized by slowly progressive inability to move the eyes and eyebrows. It is often the only feature of mitochondrial disease, in which case the term CPEO may be given as the diagnosis. In other people suffering from mitochondrial disease, CPEO occurs as part of a syndrome involving more than one part of the body, such as Kearns–Sayre syndrome. Occasionally CPEO may be caused by conditions other than mitochondrial diseases.
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.
Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene.
DNA polymerase subunit gamma-2, mitochondrial is a protein that in humans is encoded by the POLG2 gene. The POLG2 gene encodes a 55 kDa accessory subunit protein that imparts high processivity and salt tolerance to the catalytic subunit of DNA polymerase gamma, encoded by the POLG gene. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.
Mitochondrially encoded tRNA valine also known as MT-TV is a transfer RNA which in humans is encoded by the mitochondrial MT-TV gene.
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 isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI 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 threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene.
Mitochondrially encoded tRNA tyrosine also known as MT-TY is a transfer RNA which in humans is encoded by the mitochondrial MT-TY gene.
Mitochondrial DNA depletion syndrome, or Alper's disease, is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hepatopathic, or encephalomyopathic. These syndromes affect tissue in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant and some have survived into adulthood with the SUCLA2 encephalomyopathic variant. There is currently no curative treatment for any form of MDDS, though some preliminary treatments have shown a reduction in symptoms.
Sengers syndrome is a rare autosomal recessive condition characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. In some cases, they are inherited, in which case they would be called congenital. In addition, heart disease and muscle disease are prevalent, and life expectancy is short for many patients.