| Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes | |
|---|---|
| Classification and external resources | |
Basal ganglia calcification, cerebellar atrophy, increased lactate; a CT image of a person diagnosed with MELAS |
|
| ICD-9 | 277.87 |
| OMIM | 540000 |
| DiseasesDB | 8254 |
| eMedicine | ped/1406 |
| MeSH | D017241 |
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes – abbreviated to MELAS – is one of the family of mitochondrial cytopathies, which also include MERRF, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984.[1] A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent.[2] The disease can manifest in both sexes.
Contents |
MELAS is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). In most cases, the signs and symptoms of this disorder appear in childhood following a period of normal development.[3] Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).
Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, loss of bowel control, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, Epilepsy, and hormonal imbalances.
The presentation of some cases is similar to that of Kearns-Sayre syndrome.[4]
MELAS is caused by mutations in the genes in mitochondrial DNA.
Some of the genes (MT-ND1, MT-ND5) related to MELAS provide instructions for making proteins involved in normal mitochondrial function. These proteins are part of a large enzyme complex (NADH dehydrogenase, also called complex I) in mitochondria that helps convert oxygen and simple sugars to energy.
Other genes (MT-TH, MT-TL1, and MT-TV) associated with this disorder provide instructions for making molecules called transfer RNAs (tRNAs), which are chemical cousins of DNA. These molecules help assemble protein building blocks called amino acids into full-length, functioning proteins within mitochondria.
Mutations in a particular transfer RNA gene, MT-TL1, cause more than 80 percent of all cases of MELAS. These mutations impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.
This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS.
There is no known treatment for the underlying disease, which is progressive and fatal. Patients are managed according to what areas of the body are affected at a particular time. Enzymes, amino acids, antioxidants and vitamins have been used, but there have been no consistent successes reported.
Although there have been no controlled trials on long-term benefits of dietary manipulations, the following supplements have shown promise and given hope to MELAS patients.
|
||||||||||||||||||||