What is mitochondrial myopathy

Some affected children and adults are living fairly normal lives. In other cases, affected children may not survive beyond their teenage years. Adult onset can result in drastic lifestyle and physical changes in a short amount of time. Our Research Grant Program and accelerators program supports the top minds in mitochondrial medicine. As we fight to find a cure for mitochondrial disease, there are some treatments, vitamins and dietary supplements available to help alleviate symptoms and slow the disease progression.

However, the effectiveness of current treatments varies greatly. Our best hope for progressing patient care is funding mitochondrial disease research and clinical trials.

Stay informed. We All Have Mitochondria. What Is Mitochondrial Disease? Why Do Mitochondria Malfunction? How Mitochondrial Disease Affects the Body The parts of your body that need the most energy — heart, brain, muscles — are most affected by mitochondrial disease.

Pancreas diabetes, pancreatic failure, parathyroid failure. Kidneys renal tube failure. Heart defects, blockage, cardiomyopathy. The prognosis for patients with mitochondrial myopathies varies greatly, depending largely on the type of disease and the degree of involvement of various organs. These disorders cause progressive weakness and can lead to death. Skip to main content.

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Search Disorders. These treatments are nutritional supplements based on three natural substances involved in ATP production in our cells.

One substance, creatine , normally acts as a reserve for ATP by forming a compound called creatine phosphate also called phosphocreatine. In fact, creatine phosphate typically provides the initial burst of ATP required for strenuous muscle activity.

Another substance, carnitine , generally improves the efficiency of ATP production by helping import certain fuel molecules into mitochondria and cleaning up some of the toxic byproducts of ATP production. Carnitine is available as an over-the-counter supplement called L-carnitine. Finally, coenzyme Q10 , also called CoQ10 or ubiquinone, is a component of the mitochondrial respiratory chain which uses oxygen to manufacture ATP.

CoQ10 is also an antioxidant. Some mitochondrial diseases are caused by CoQ10 deficiency, and CoQ10 supplementation is clearly beneficial in these cases. It might provide some relief from other mitochondrial diseases. Although there is a need for careful studies to confirm the value of this treatment, some people with mitochondrial disease have reported modest benefits. The inheritance of mitochondrial diseases is complex, and often a mitochondrial myopathy can be difficult to trace through a family tree.

In fact, many cases of mitochondrial disease are sporadic, meaning that they occur without any family history. To understand how mitochondrial diseases are inherited, it is important to know that there are two types of genes essential to mitochondria.

The first type is housed within the nucleus—a compartment within our cells that contains most of our genetic material, or DNA. The second type resides exclusively within DNA contained inside the mitochondria. Nuclear DNA is packaged into structures called chromosomes—22 pairs of non-sex related chromosomes called autosomes and a single pair of sex chromosomes XX in females and XY in males.

This means that except for genes on the X chromosome, everyone has two copies of the genes in nDNA, with one copy inherited from each parent. There are three inheritance patterns seen for diseases caused by nDNA mutations:. Mitochondrial diseases caused by mtDNA mutations are unique because they are inherited in a maternal pattern.

A mother can pass defective mtDNA to any of her children, but only her daughters—and not her sons—will pass it to the next generation. Another unique feature of mtDNA diseases arises from the fact that a typical human cell contains only one nucleus but hundreds of mitochondria. The risk of passing on a mitochondrial disease to a child depends on many factors, including whether the disease is caused by mutations in nDNA or mtDNA.

To find out more about these risks, talk with a doctor or genetic counselor. Features: Typical symptoms include cardiomyopathy, general muscle weakness, and a low white blood cell count, which leads to an increased risk of infection. This syndrome was once considered uniformly fatal in infancy, but some individuals are now living much longer.

Chronic progressive external ophthalmoplegia cPEO Onset: usually in adolescence or early adulthood. Features: PEO is often a symptom of mitochondrial disease. In some people, it is a chronic, slowly progressive condition associated with instability to move the eyes and general weakness and exercise intolerance. Other common symptoms include cardiomyopathy, conduction block a type of cardiac arrhythmia ataxia, short stature, neuropathy, and deafness.

Features: Brain abnormalities that can result in abnormal muscle tone, ataxia, seizures, impaired vision and hearing, developmental delays, and respiratory problems. Infants with the disease have a poor prognosis. Features: A myopathic form of MDDS is characterized by weakness that eventually affects the respiratory muscles. Some forms of MDDS, such as Alpers syndrome, are marked by brain abnormalities and progressive liver disease.

The anticonvulsant sodium valproate should be used with caution in children with Alpers syndrome because it can increase the risk of liver failure. However, the episodes can produce stroke-like symptoms in the short term such as temporary vision loss, difficulty speaking, or difficulty understanding speech and lead to progressive brain injury. The cause of the stroke-like episodes is unclear. Features:This disorder is characterized by PEO, ptosis, limb weakness, and gastrointestinal digestive problems, including vomiting, chronic diarrhea, and abdominal pain.

Another common symptom is peripheral neuropathy a malfunction of the nerves that can lead to sensory impairment and muscle weakness. The disease also can cause hearing impairment and short stature.

In addition to the core symptoms for which it is named, NARP can involve developmental delay, seizures, and dementia. Retinitis pigmentosa refers to a degeneration of the retina in the eye, with resulting loss of vision. Inheritance pattern: maternal. Diagnosis and management of mitochondrial disease: a consensus statement from the mitochondrial medicine society. Genet Med. Some vitamins, are mainly used as part of an antioxidant cocktail, for example, thiamine, vitamin C, and vitamin E.

Thiamine, often used to treat patients with pyruvate dehydrogenase PDH deficiency, is known to enhance the activity of PDH and increase the availability of pyruvate for oxidation. Treatment of mitochondrial disorders. Biotin is a water-soluble vitamin that serves as an essential coenzyme for 5 carboxylases. Biotin and biotinidase deficiency.

Expert Rev Endocrinol Metab. Both, biotin and thiamine are used in treatment of biotin-responsive basal ganglia disease caused by mutations in SLC19A3 gene. Novel SLC19A3 promoter deletion and allelic silencing in biotin-thiamineresponsive basal ganglia encephalopathy. PLoS One. Furthermore, biotin is also used in patients with biotinidase deficiency mutations, which is known to mimic Leigh syndrome. For this reason, frequent measurement of vitamin D levels in blood is recommended, and if applicable, vitamin D substitution should be ensured.

Leber hereditary optic neuropathy is most frequently caused by one of the following mtDNA mutations: m. Most LHON patients remain asymptomatic until early adulthood when visual loss may be sudden and profound.

Often asymmetric in onset, the visual loss can be triggered by smoking and possibly alcohol. The marked decrease in visual acuity experienced during the acute phase of LHON is thought to be a consequence of respiratory chain dysfunction in viable, but inactive, retinal ganglion cells. Leber hereditary optic neuropathy: respiratory chain dysfunction and degeneration of the optic nerve. Vision Res. Idebenone is known to preserve or reestablish retinal ganglion cell function during the acute phase and thus protects from irreversible retinal ganglion cell loss.

Accordingly, the European Medicines Agency has subsequently licensed Raxone idebenone to treat adults and adolescents aged 12 years and older at a recommended daily dose of mg. Treatment should begin immediately after diagnosis and continue, if possible, for at least 2 years. Stoke-like episodes in MELAS syndrome usually occur before the age of 40 years and are 1 cardinal clinical feature of this condition. Hemianopsia or cortical blindness are often the first focal neurological disturbances, and the episodes are often accompanied by migraine-like headaches with vomiting and epileptic seizures.

Nitric oxide NO donors, such as L-arginine and citrulline, may be a therapeutic option for MELAS-related stroke-like episodes, and research studies are ongoing.

These NO donors may reduce the severity of stroke-like episodes and reduce the frequency of the episodes. However, there are only a few clinical trials investigating L-arginine, and the window of opportunity for treatment with L-arginine is limited within 12 hours of onset. Dichloroacetate DCA is a synthetic agent aimed to increase the respiratory chain substrate availability, so as to keep the PDH complex in an active state and reduce the accumulation of lactate in body tissues.

Dichloroacetate is used to treat lactic acidosis, a common problem in mitochondrial disorders. However, treatment with DCA leads to irreversible peripheral neuropathy. Controlled trials did not lead to conclusive evidence of the benefits of DCA in patients with mitochondrial disorders, but individual case reports suggest some benefit from using DCA as a treatment option. EPI is a synthetic analogue of vitamin E para-benzoquinone , targeting the repletion of reduced intracellular glutathione.

EPI reverses the progression of the pediatric mitochondrial disease — genetically defined Leigh syndrome. Mol Genet Metab. There are some studies showing that treatment with EPI in patients with Leigh syndrome subacute necrotizing encephalopathy improved the clinical outcome.

Initial experience in the treatment of inherited mitochondrial disease with EPI Mitochondrial DNA mutations tend to be present in a heteroplasmic state.

Therefore, one therapeutic approach is the elimination or reduction of mutated mtDNA amount below the threshold at which the disease biochemically or clinically manifests.

Gen Ther. Manipulating mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease. Hum Mol Genet. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. Nat Med. However, one limitation was the severe cellular depletion of mtDNA before repopulation with favorable heteroplasmy ratio.

According to cell and zebra fish model studies, a genetic or small molecule activation of hypoxia response is protective against mitochondrial toxicity.

Hypoxia as a therapy for mitochondrial disease. Limiting oxygen availability has been found to be a protective factor during respiratory chain inhibition. In a genetic mouse model of Leigh syndrome, it could be shown that chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers.

MNGIE is clinically characterized by CPEO, severe gastrointestinal dysmotility leading to cachexia, peripheral neuropathy, and leukoencephalopathy, usually leading to death in early to mid-adulthood. Mitochondrial neurogastrointestinal encephalomyopathy MNGIE : clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. The genetic basis of this disease is a loss-offunction mutation in the TYMP gene encoding for the cytosolic enzyme thymidine phosphorylase TPase , which leads to severe elevations of thymidine and deoxyuridine in blood and other tissues, likely disrupting the dinucleotide pool available for mtDNA synthesis and causing instability of the mtDNA that results in multiple deletions, depletion, and point mutations.

Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy MNGIE. FEBS Lett. Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice.

Approaches to eliminate thymidine and deoxyuridine in blood and other tissues only showed positive results transiently. Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem.