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MELAS Syndrome Fast Facts

MELAS syndrome is a disorder that affects many different parts of the body, but its most pronounced effects are on the central nervous system (brain and spinal cord) and the muscles.

MELAS usually begins in childhood, but some cases have emerged in adulthood.

MELAS can cause various symptoms, including seizures, muscle weakness, paralysis, and stroke-like episodes.

The disorder typically causes progressive, life-threatening complications. Life expectancy varies, but MELAS is usually fatal between the ages of 10 and 35.

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MELAS can cause various symptoms, including seizures, muscle weakness, paralysis, and stroke-like episodes.

What is MELAS Syndrome?

MELAS syndrome is a rare disorder that affects the brain, central nervous system, muscles, and other parts of the body. The disorder’s name is Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS). It is characterized by nerve and muscle tissue degeneration, a buildup of lactic acid throughout the body, and recurrent stroke-like episodes that may cause brain damage.

The disorder typically begins in childhood, between 2 and 15, although some cases have begun in adulthood.

Symptoms of MELAS Syndrome

MELAS can produce a wide range of symptoms that affect many parts of the body. Brain- and muscle-related symptoms are typical, and excess lactic acid can produce distinct systemic symptoms.

Symptoms related to the brain and muscles may include:

  • Problems with thought processes and concentration
  • Behavioral changes
  • Speech difficulties
  • Seizures
  • Hallucinations
  • Muscle weakness
  • Paralysis

Lactic acid buildup may cause various symptoms, including:

  • Vomiting
  • Abdominal pain
  • Weakness and fatigue
  • Severe cramps
  • Breathing problems

MELAS also causes episodes with symptoms resembling those of a stroke, including:

  • Slurred speech
  • Loss of feeling or tingling on one side of the body
  • Dizziness
  • Trouble concentrating or confusion
  • Double vision, vision loss, or hearing loss
  • Problems with balance or coordination

What Causes MELAS Syndrome?

MELAS is caused by abnormal changes (mutations) in genes vital for the function of mitochondria, microscopic structures inside cells that generate energy. The gene mutations cause deficiencies of crucial proteins without which mitochondria can’t function properly. Impairment of mitochondrial function leads to the symptoms of MELAS, although scientists don’t yet know precisely how.

It is common for the gene mutations associated with MELAS to affect mitochondria in some cells more than others. If a cell, or group of cells, contains a relatively high proportion of normal mitochondria, those cells will be less affected. This helps explain why the disorder affects some parts of the body and not others. In general, the cells most affected seem to have the highest energy requirements, including the brain, muscles, and eyes.

Is MELAS Syndrome Hereditary?

MELAS is inherited in most cases. Researchers have identified more than a dozen different mutations associated with the disorder, but about 80% of cases are associated with a mutation in the MT-TL1 gene.

The disorder is inherited in a mitochondrial pattern, also known as a maternal pattern. The gene mutations associated with MELAS lie in DNA contained only in the mitochondria (mtDNA). These genes are inherited only from the mother, so all inherited cases of MELAS are inherited from a child’s mother. Sperm cells do not contribute mtDNA to a developing embryo, so the disorder can’t be inherited from the father. However, MELAS can be inherited by both males and females.

In a small number of cases, MELAS occurs when there is no family history of the disorder. These cases seem to be caused by a gene mutation that happens spontaneously during the early development of an embryo.

How Is MELAS Syndrome Detected?

Children with MELAS tend to develop normally before symptoms begin. Symptoms most commonly first appear between the ages of 2 and 10, although the disorder may start in infancy in rare cases.

Early signs in infancy may include:

  • Slow growth
  • Deafness

Early signs in childhood may include:

  • Poor appetite
  • Vomiting
  • Migraine-like headaches
  • Seizures
  • Weakness or difficulty tolerating exercise
  • Short stature

How Is MELAS Syndrome Diagnosed?

A doctor may suspect MELAS if a child presents the disorder’s characteristic symptoms, particularly its stroke-like episodes. Diagnostic procedures will aim to rule out other potential causes for the symptoms and confirm a diagnosis of MELAS.

Diagnostic steps may include:

  • A physical exam. This exam will be aimed at ruling out physical conditions that could be causing the symptoms.
  • Muscle biopsy. This test examines a sample of muscle tissue, which will usually show the presence of distinctive fibers in the case of MELAS.
  • Laboratory tests. Various tests may be used to look for signs of MELAS, such as excess lactic acid in the muscles or elevated protein levels in the cerebrospinal fluid (CSF).
  • Magnetic resonance imaging (MRI). This imaging exam may be used to look for stroke-like damage to the brain.
  • Electrocardiogram/echocardiogram. These tests may be used to look for heart abnormalities.
  • Genetic testing. These tests can identify the mtDNA mutations associated with MELAS.

How Is MELAS Syndrome Treated?

MELAS has no cure, and no treatment will reverse the effects of its symptoms. Treatment approaches vary depending on the symptoms present. Medications and therapies focus on reducing the impact of symptoms and preventing complications.

Potential treatment options include:

  • Anti-convulsant medications to control seizures
  • Coenzyme q10 and L-carnitine may improve symptoms in some cases
  • Arginine to treat stroke-like episodes
  • Cochlear implants for deafness
  • Appropriate exercise as directed by a doctor

How Does MELAS Syndrome Progress?

Degeneration of muscle tissue, nerve tissue, and other vital organs typically causes progressively worsening symptoms in people with MELAS. The disorder’s stroke-like episodes also cause damage to the brain, often resulting in neurological problems. These complications can be life-threatening, and the condition is typically fatal by late childhood or early adulthood.

Long-term effects of MELAS may include:

  • Loss of movement abilities
  • Loss of speech abilities
  • Dementia
  • Vision loss
  • Hearing loss
  • Heart problems
  • Kidney problems
  • Diabetes
  • Digestive problems

How Is MELAS Syndrome Prevented?

MELAS cannot be prevented. People with a family history of the disorder are advised to consult with a genetic counselor to assess their risk if they plan to have children.

MELAS Syndrome Caregiver Tips

Many people with MELAS also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with MELAS and other mitochondrial diseases:

MELAS Syndrome Brain Science

The brain-related episodes characteristic of MELAS resemble strokes, which are caused by disruption of blood flow to the brain, but the MELAS episodes differ from strokes in several ways, including:

  • The episodes are not confined to an area served by specific blood vessels as with a stroke.
  • The evidence of the episode on an MRI scan may change or resolve more quickly than that of a stroke and may differ in other ways.

Effects of the episodes often include weakness or paralysis on one side of the body, loss of vision in part of the visual field (hemianopia), and loss of speech abilities (aphasia).

Some scientists believe that a deficiency of nitric oxide in the brain may cause small blood vessels to constrict, leading to stroke-like episodes.

MELAS Syndrome Research

Title: A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy (MIT-E)

Stage: Recruiting

Principal investigator: Dr. Richard Haas

University of California

San Diego, CA  

This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completing the randomized, placebo-controlled phase, participants may enter a 48-week, long-term extension phase during which they will receive open-label treatment with vatiquinone.

 

Title: North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) (NAMDC)

Stage: Recruiting

Study Director: Michio Hirano, MD

Columbia University

New York, NY

Mitochondrial diseases comprise a group of relatively rare (~1 in 5000 adults) but very serious genetic disorders. Mitochondria are often called the “powerhouses of the cell” because they provide the energy our cells need to live. Mitochondria have their own DNA (mtDNA), but they also rely on DNA from the cell nucleus (nDNA). Mutations cause mitochondrial diseases in either mitochondrial or nuclear DNA that result in poorly functioning mitochondria. This can cause a variety of symptoms, including muscle weakness, seizures, mental retardation, dementia, hearing loss, blindness, strokes, diabetes, and premature death. Unfortunately, most mitochondrial diseases are progressive, and we are unable to cure most of these diseases with currently available treatments.

Research into mitochondrial diseases has been hampered by the low frequency of these disorders and by under-diagnosis by clinicians. This has hindered patient recruitment for research studies and clinical trials. The North American Mitochondrial Disease Consortium (NAMDC) was established to help surmount these issues. Led jointly by Drs. Michio Hirano and Salvatore DiMauro, NAMDC is a consortium of clinicians and researchers interested in mitochondrial disease research in the United States and Canada.

By creating a mechanism for sharing patient samples with researchers, data, and patient contact information, NAMDC will make it easier to conduct clinical and basic laboratory research.

Patient information will be shared through the “Patient Data Registry,” a specially-designed database, and patient tissue samples will be shared through the use of the “Patient Sample Biorepository,” a storage facility in which patient-derived biological samples will be maintained. The Registry and the Biorepository will hopefully accelerate progress in the understanding and treatment of mitochondrial disease.

Patients can enroll at any of the NAMDC member sites. A web-based remote enrollment is also available at www.namdc.org for eligible patients who reside far from any of the NAMDC participating locations.

 

Title: L-Citrulline Dose-Finding Safety Study in MELAS

Stage: Recruiting

Principal investigator: Fernando Scaglia, MD

Baylor College of Medicine

Houston, TX

The human body is made of many cells, and each cell contains many mitochondria. Mitochondria are called the cell’s powerhouses because they produce the energy needed for a cell to be healthy and function the way it is intended to.

Diseases of the mitochondria affect the way the tissues and cells of the body make and use energy and can affect almost all the different organs of the body, like the brain and the muscles.

MELAS syndrome is one of the mitochondrial diseases; patients with this disease have different complications, including stroke-like episodes, headache, muscle weakness, fatigue, and hearing loss. One of the factors contributing to complications seen in patients with MELAS syndrome, particularly the stroke-like episodes, is decreased amount of an element called nitric oxide. This element is made in the body from an amino acid called arginine. Amino acids are the building blocks of proteins. Proteins make the muscles in the body, and they are present in meat, chicken, and fish.

In this study, the highest acceptable dose of an amino acid called citrulline will be established in participants who have a mitochondrial disorder. Previous research conducted by several groups, including Baylor College of Medicine, has determined there is a deficiency of a compound called nitric oxide in patients affected with MELAS.

The lack of nitric oxide could cause constriction of blood vessels in the brain, making it easier for these patients to have a metabolic stroke. The amino acid citrulline is a foundation for nitric oxide. In earlier studies, the investigator found more nitric oxide production in the body when participants affected with MELAS took L-citrulline.

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