MELAS Syndrome
MELAS syndrome is a rare inherited condition that primarily affects the nervous system and muscles, usually appearing in childhood and causing stroke-like episodes, seizures, and a buildup of lactic acid in the body.
Table of contents
- What is MELAS syndrome?
- How common is MELAS syndrome?
- What causes MELAS syndrome?
- What are the symptoms?
- How is MELAS syndrome diagnosed?
- How is MELAS syndrome treated?
- What are the complications?
- What is the outlook?
What is MELAS syndrome?
MELAS syndrome is a rare genetic condition that affects many parts of the body, particularly the brain, nervous system, and muscles. The name MELAS stands for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, which describes the main features of this condition[1].
Mitochondria are tiny structures inside most cells that work like power plants, converting food into energy that cells can use. In MELAS syndrome, changes in the genetic instructions for building mitochondria mean they cannot work properly[1]. When cells cannot produce enough energy, especially in organs that need a lot of power like the brain and muscles, serious problems develop.
Although people are born with the genetic changes that cause MELAS, symptoms typically do not appear immediately. Most people show signs of the condition by or before age 20, though symptoms can sometimes begin before age 2 or after age 40[1][3]. Children with MELAS often develop normally at first, then symptoms appear during childhood, usually between ages 2 and 15[2].
How common is MELAS syndrome?
MELAS syndrome is rare, with an estimated occurrence of about 1 in 4,000 people[1]. Some studies suggest the condition affects between 1 and 16 out of every 100,000 adults[3]. Although it is rare, MELAS is one of the most common types of mitochondrial diseases, which are conditions affecting how mitochondria function[3].
The condition can affect anyone regardless of gender or ethnicity. However, only women can pass the condition on to their children because mitochondrial DNA is inherited only from mothers[1][4].
C536567
G31.81
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes; Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
What causes MELAS syndrome?
MELAS syndrome is caused by changes (called mutations or variants) in genes that contain instructions for building mitochondria. Most of these genes are located in mitochondrial DNA, which is separate from the DNA found in the cell’s main control center[4].
About 80% of people with MELAS have a specific genetic change in a gene called MT-TL1, where an A is changed to a G at position 3243 (written as m.3243A>G)[2][4]. Other genetic changes in different mitochondrial genes can also cause MELAS, including changes in genes called MT-ND1, MT-ND5, MT-TH, and MT-TV[4][3].
These genetic changes affect the mitochondria’s ability to make proteins, use oxygen, and produce energy. Some genes provide instructions for making proteins involved in energy production, while others help assemble amino acids (protein building blocks) into functioning proteins within mitochondria[4].
Because mitochondrial DNA is passed down only from mothers through egg cells, children inherit MELAS from their mothers. This pattern is called maternal inheritance[4]. Less commonly, the genetic changes can occur randomly before birth without being inherited[4].
What are the symptoms?
Because mitochondria are found in nearly all cells, MELAS syndrome can affect many different organs and tissues throughout the body, causing a wide range of symptoms[1].
Stroke-like episodes
The hallmark feature of MELAS is stroke-like episodes, which are sudden events that resemble strokes. These episodes can cause temporary muscle weakness on one side of the body, altered consciousness, vision problems, seizures, and severe headaches similar to migraines[4][3]. Most people with MELAS experience these episodes before age 40[4]. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, movement problems, and loss of thinking abilities[4].
Nervous system and brain symptoms
Symptoms affecting the brain and nervous system include[1]:
- Seizures
- Confusion and changes in behavior
- Headaches
- Dizziness or loss of balance
- Numbness or tingling on one side of the body
- Slurred words and speech problems
- Vision problems like double vision or loss of vision
- Weakness or paralysis (inability to move parts of the body)
Lactic acid buildup
Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Lactic acid is normally produced when the body makes energy, but in MELAS it accumulates to harmful levels[1][4]. This can lead to[4]:
- Vomiting and stomach pain
- Extreme tiredness (fatigue)
- Muscle weakness and cramping
- Difficulty breathing
Other common symptoms
Additional symptoms that often occur include[1][3][4]:
- Short stature (being shorter than average)
- Hearing loss or impairment
- Diabetes
- Muscle pain and weakness
- Loss of appetite
- Learning disabilities
- Heart and kidney problems
- Involuntary muscle spasms
- Impaired muscle coordination
- Hormonal imbalances
Almost all people with MELAS develop diabetes and hearing loss before brain-related symptoms begin[1].
How is MELAS syndrome diagnosed?
Diagnosing MELAS syndrome typically begins with a healthcare provider taking a detailed medical history and asking about symptoms. They will also ask about family history, especially whether the mother has similar symptoms or a diagnosis of MELAS[1][5].
Genetic testing
The only way to definitively diagnose MELAS is through genetic testing, which looks for the specific changes in mitochondrial DNA that cause the condition[5][3]. This testing can be done on blood samples or other tissues.
Other diagnostic tests
Healthcare providers may perform several other tests to help diagnose MELAS and understand how it affects the body[1][3]:
- Blood and urine tests to measure levels of lactic acid and other substances
- Cerebrospinal fluid testing, where fluid surrounding the brain and spinal cord is sampled through a procedure called lumbar puncture
- Imaging tests like magnetic resonance imaging (MRI) or computed tomography (CT) scans to look at the brain and detect damage
- Muscle biopsy, where a small sample of muscle tissue is removed and examined under a microscope. In MELAS, the tissue often shows characteristic abnormalities called “ragged red fibers”[5]
How is MELAS syndrome treated?
Currently, there is no cure for MELAS syndrome, and no treatment has been proven to slow or stop the progression of the disease[2][3]. However, various treatments can help manage symptoms and improve quality of life for people with MELAS and their families.
Emergency treatment for stroke-like episodes
L-arginine is one of the most promising treatments for MELAS. People experiencing stroke-like episodes should receive intravenous (through a vein) arginine as soon as possible to reduce brain damage. Healthcare providers typically give a loading dose followed by continuous infusion for several days[3]. Taking L-arginine regularly may also help prevent future stroke-like episodes[3].
L-citrulline works similarly to L-arginine and may also be helpful[1].
Seizure management
Anti-seizure medications can help control seizures in people with MELAS. However, one specific medication called valproate should be avoided as it may worsen mitochondrial function[1][3].
Vitamins and supplements
Several vitamins and supplements may provide general benefits for some individuals, though evidence of their effectiveness varies[1][3]:
- Coenzyme Q10 (also called CoQ10) may help increase energy production in mitochondria
- L-carnitine may improve mitochondrial function
- Other supplements that have been tried include riboflavin (vitamin B2), nicotinamide, and idebenone
Other supportive treatments
Additional treatments focus on managing specific symptoms and complications[3]:
- Insulin for diabetes
- Cochlear implants for severe hearing loss
- Moderate supervised exercise for muscle weakness
- Physical and occupational therapy
Because MELAS is inherited, genetic counseling may be recommended for families to understand the risks of passing the condition to future children[3].
What are the complications?
MELAS syndrome can lead to several serious complications over time[1]:
- Intellectual disability and possible dementia (progressive loss of thinking abilities)
- Diabetes
- Severe hearing problems
- Muscle problems including spasms and lack of control
- Difficulty walking and maintaining balance
- Loss of vision
- Liver problems
The condition is characterized by progressive deterioration of the nervous system, leading to neurological impairment that typically worsens during adolescence or early adulthood[2].
What is the outlook?
MELAS syndrome is a progressive condition, meaning symptoms typically worsen over time. The progression and severity can vary considerably from person to person, even within the same family[4].
Most people with MELAS survive approximately 17 years after the onset of seizures or other nervous system problems[3]. The condition is often fatal, though the timeline varies greatly among individuals. Repeated stroke-like episodes can cause cumulative damage to the brain, leading to progressive disability.
While there is currently no cure, ongoing research continues to search for better treatments. Clinical trials are actively testing new medications and approaches that may help people with MELAS. Support from healthcare teams including neurologists, geneticists, physical therapists, and other specialists can help manage symptoms and maintain the best possible quality of life[2].
