Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes

Synonyms

5

Overview

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. 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, 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, and hormonal imbalances.

Symptoms

Symptoms typically begin in childhood and 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.

Symptoms:

  • Abnormality of mitochondrial metabolism
  • Cerebral ischemia
  • Developmental regression
  • EMG abnormality
  • Hemiplegia/hemiparesis
  • Migraine
  • Muscle weakness
  • Myopathy

Causes

People with MELAS can also have a buildup of lactic acid in their bodies that can lead to vomiting, abdominal pain, fatigue, muscle weakness, and difficulty breathing. The genes associated with MELAS are located in mitochondrial DNA and therefore follow a maternal inheritance pattern (also called mitochondrial inheritance). MELAS can be inherited from the mother only, because only females pass mitochondrial DNA to their children. In some cases, MELAS results from a new mutation that was not inherited from a person's mother.

This type of inheritance applies to all conditions caused by genes in mtDNA. Mitochondria are structures in each cell that turn molecules into energy, and each contain a small amount of DNA. Only egg cells (not sperm cells) contribute mitochondria to offspring, so only females can pass on mitochondrial mutations to their children. Conditions resulting from mutations in mtDNA can appear in every generation of a family and can affect both males and females. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the condition results from a new mutation in a mitochondrial gene and occurs in an individual with no history of MELAS in the family.

While most of our DNA is in the chromosomes in the cell nucleus, some of our DNA is in another important structure called the mitochondrion. The mitochondria are located outside the nucleus in the cell's cytoplasm. Each mitochondrion has a chromosome made of DNA that is quite different from the better known chromosomes in the nucleus. The mitochondrial chromosome is much smaller; it is round; there are many copies of the mitochondrial chromosome in every cell; and no matter whether we are male or female, we inherit all of our mitochondrial chromosome from our mother. Much of the DNA in our mitochondria is used to manufacture proteins involved in the key function of mitochondria -- to produce energy and power the cells in our body.


Diagnosis

The diagnosis of MELAS syndrome is usually suspected on clinical grounds. However, confirmation of the diagnosis usually requires a muscle or brain biopsy. The muscle biopsy shows characteristic ragged red fibers; a brain biopsy shows stroke-like changes.

Prognosis

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.

  • CoQ10 has been helpful for some MELAS patients. Nicotinamide has been used because complex l accepts electrons from NADH and ultimately transfers electrons to CoQ10.
  • Riboflavin has been reported to improve the function of a patient with complex l deficiency and the 3250T-C mutation.
  • The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impairment of vasodilation in intracerebral arteries due to nitric oxide depletion.
  • There is also a case report where succinate was successfully used to treat uncontrolled convulsions in MELAS patients, although this treatment modality is yet to be thoroughly investigated or widely recommended.

Treatment

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. Antioxidants and vitamins have been used, but there have been no consistent successes reported.

Resources

  • NIH
  • Genetics Home Reference