DECODING MELAS SYNDROME: SYMPTOMS, COMPLICATIONS, TREATMENT, AND MORE
Medically Reviewed by Dr. Sony Sherpa (MBBS)
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder that primarily affects the nervous system and muscles. It results from genetic mutations in mitochondrial DNA (mtDNA), leading to impaired energy production at the cellular level. This disorder manifests with a wide range of symptoms, including neurological and muscular impairments.
MELAS syndrome is estimated to affect approximately 1 in 4,000 people worldwide. Symptoms most often appear in childhood or early adulthood, although late-onset cases have been documented. Symptoms typically begin between ages 2 and 15 and may worsen over time.
What is MELAS Syndrome?
Mitochondria, often called the cell’s powerhouse, generate adenosine triphosphate (ATP), the essential energy source that powers cellular functions. In MELAS, genetic mutations impair mitochondrial function, leading to reduced ATP production, increased oxidative stress, and lactic acid buildup in the blood. These disruptions contribute to the hallmark symptoms of the disorder, such as muscle weakness, neurological impairment, and metabolic imbalances.
MELAS syndrome is primarily caused by mutations in mitochondrial DNA (mtDNA), with the most common mutation occurring in the MT-TL1 gene (m.3243A>G). This mutation affects the transfer RNA for leucine, disrupting protein synthesis and mitochondrial function.
MELAS follows a maternal inheritance pattern, meaning that the disorder is passed down exclusively from the mother. Mitochondrial DNA, unlike nuclear DNA, is inherited only from the mother. As a result, all offspring of an affected mother have the potential to inherit the mutation, while fathers do not pass on mitochondrial disorders.
Although MELAS typically presents in childhood, late-onset cases have been reported. Adults with late-onset MELAS may experience progressive neurological symptoms, including stroke-like episodes and cognitive decline, often leading to misdiagnosis.
MELAS Syndrome Symptoms
MELAS syndrome presents with a variety of symptoms affecting multiple organ systems. The severity and progression of symptoms vary among people.
Neurological Problems
- Recurrent Stroke-like episodes (SLEs): These episodes can cause hemiparesis (weakness on one side of the body), vision loss, and seizures.
- Encephalopathy: Brain dysfunction that may lead to cognitive decline and behavioral changes.
- Headaches: Chronic or severe migraines are common.
- Seizures: Can occur independently or as part of a stroke-like episode.
- Dementia: Progressive cognitive impairment affecting memory and executive functions.
Muscle Weakness (Myopathy)
- Exercise intolerance: Difficulty sustaining physical activity due to low energy production.
- Muscle pain: Chronic discomfort or cramps, especially during exertion.
- Fatigue: Persistent tiredness due to inefficient ATP production.
Lactic Acidosis
- Metabolic disturbance: Lactic acid buildup in the blood can cause muscle weakness and worsen fatigue.
Other Common Features
- Short stature: Growth impairment due to metabolic dysfunction.
- Hearing loss: Sensorineural hearing impairment is common due to mitochondrial dysfunction in auditory cells.
- Diabetes mellitus: Impaired glucose metabolism leading to diabetes.
- Cardiomyopathy: Heart muscle abnormalities that can cause arrhythmias and heart failure.
- Gastrointestinal issues: Symptoms such as vomiting, and abdominal pain.
- Gastrointestinal Dysmotility: Patients often experience severe nausea, vomiting, and gastroparesis due to autonomic dysfunction.
Complications of MELAS Syndrome
MELAS is a progressive disorder that can lead to severe complications affecting multiple organ systems. Some of the most significant complications include:
- Kidney Dysfunction: Mitochondrial nephropathy can lead to renal failure in some patients.
- Vision Impairment: Recurrent stroke-like episodes may cause cortical blindness or optic atrophy.
- Gastrointestinal complications: chronic intestinal pseudo-obstruction (IPO), pancreatitis, gastroparesis and hepatopathy.
- Development of psychiatric conditions such as depression with psychotic features, schizophrenia, or bipolar disorder.
- Cognitive impairment: Difficulty with concentration, memory, and learning.
- Autism spectrum disorders.
MELAS Syndrome and Anesthesia Considerations
Patients with MELAS syndrome require specialized care when undergoing anesthesia due to their impaired mitochondrial function. Key considerations include:
- Risk of Metabolic Crisis – Anesthesia can increase metabolic stress, leading to lactic acidosis, respiratory failure, and prolonged recovery.
- Avoidance of Certain Anesthetics – Volatile anesthetics can exacerbate mitochondrial dysfunction and should be used with caution.
- Use of Alternative Agents – Total intravenous anesthesia (TIVA) may be preferred.
- Monitoring for Cardiovascular Instability – Due to the risk of arrhythmias and hypotension, continuous cardiac monitoring is essential.
- Postoperative Support – Patients may require extended recovery time, respiratory support, and close metabolic monitoring post-surgery.
Diagnosis of MELAS Syndrome
Diagnosis of MELAS is based on the characteristic combination of symptoms, including recurrent stroke-like episodes, lactic acidosis, muscle weakness, and progressive neurological decline.
Laboratory tests can help identify metabolic abnormalities associated with MELAS:
- Lactic Acid Levels – Elevated in both blood and cerebrospinal fluid
- Muscle Enzymes – Creatine kinase (CK) may be elevated
- Genetic Testing – Confirms mutations in mtDNA, particularly the m.3243A>G mutation
Neuroimaging
MRI scans reveal brain abnormalities typical of MELAS, including:
- Stroke-like lesions that do not follow vascular territories
- White matter changes
- Cortical and subcortical atrophy
Muscle Biopsy
A muscle biopsy can provide further diagnostic confirmation by identifying the following:
- Ragged Red Fibers (RRF) – A hallmark of mitochondrial disease
- Mitochondrial proliferation and structural abnormalities
Cerebrospinal Fluid Analysis
Analysis of cerebrospinal fluid (CSF) can show elevated lactate levels, supporting the diagnosis of MELAS.
Diagnostic Criteria
According to established criteria, MELAS diagnosis should be suspected in people with:
- Stroke-like episodes before age 40
- Lactic acidosis
- Presence of ragged red fibers (RRF) in muscle biopsy
Differential Diagnosis
MELAS must be distinguished from other mitochondrial disorders, including:
- Kearns-Sayre Syndrome – Kearns-Sayre syndrome is distinguished from MELAS by heart disease such as heart block as well as the characteristic visual findings:
- progressive weakness of certain eye muscles (chronic progressive external ophthalmoplegia);
- abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), leading to chronic inflammation, progressive degeneration, and wearing away of certain eye structures (pigmentary degeneration of the retina)
- MERRF Syndrome (Myoclonus Epilepsy associated with Ragged-Red Fibers) – While MERRF and MELAS have overlapping symptoms, including seizures, cognitive decline, and muscle weakness, genetic testing is crucial for accurate differentiation.
- Leigh Disease – Leigh disease is a rare, inherited disorder that affects the nervous system. It causes progressive damage to the brain, spinal cord, and optic nerves. Symptoms typically appear in infancy or early childhood, often between three months and two years of age. Children may experience a decline in motor skills, feeding difficulties, irritability, and seizures. As the disease progresses, muscle weakness, low muscle tone, and episodes of lactic acidosis can occur, potentially impacting breathing and kidney function.
MELAS Syndrome Treatment
Currently, there is no cure for MELAS, so treatment focuses on managing symptoms and improving quality of life through a multidisciplinary approach.
Symptom Management
- Stroke-like episodes: Anticonvulsants are used to manage seizures, while other medications may help reduce brain swelling.
- Muscle weakness: Physical therapy, occupational therapy, and carefully monitored exercise help maintain muscle function.
- Lactic acidosis: Dietary modifications, including a low-carbohydrate or ketogenic diet in some cases, and supplements such as Coenzyme Q10 and carnitine may help manage lactic acid buildup.
- Medications: Arginine, Coenzyme Q10, and carnitine are commonly used to support mitochondrial function.
- Other symptoms: Management of diabetes, hearing loss, heart problems, and other associated conditions is essential.
- Vaccinations: Patients should receive all childhood vaccines as well as COVID-19, pneumonia, and flu vaccinations.
Supportive Care
- Nutritional support: Avoiding dietary triggers and optimizing mitochondrial function through specific dietary strategies is important.
- Cochlear implants: Used for sensorineural deafness.
- Genetic counseling: Provides support for patients and families in understanding the hereditary aspects of MELAS.
- Speech therapy: Recommended if speech is affected due to neurological complications.
Contraindications
- Valproic Acid/Sodium Valproate: Valproic acid and sodium valproate are contraindicated in patients with MELAS syndrome due to their potential to exacerbate mitochondrial dysfunction. These drugs can increase the risk of metabolic decompensation and seizures in people with MELAS.
- Dichloroacetate: Dichloroacetate is another contraindicated treatment, as it may interfere with mitochondrial function. Its use has been associated with potential side effects in patients with mitochondrial diseases like MELAS, particularly in affecting the nervous system and metabolic pathways.
Living with MELAS
- Prognosis: MELAS is a progressive disorder, meaning its symptoms worsen over time. The condition often leads to disability, including stroke-like episodes, seizures, and organ dysfunction. Life expectancy can vary widely, with many people facing a reduced lifespan due to complications from heart, kidney, or neurological issues. Prognosis is highly individualized, depending on the severity of the symptoms and how early interventions are made.
- Management Strategies: Managing MELAS focuses on alleviating symptoms and improving quality of life. Key strategies include:
- Pacing Activities: Taking frequent breaks and avoiding overexertion can help conserve energy and reduce fatigue.
- Avoiding Stress: Stress can trigger episodes, so managing stress levels is important.
- Adequate Rest: Ensuring enough sleep and rest helps the body cope with fatigue and reduce the impact of neurological symptoms.
- Lifestyle Recommendations:
- Avoid Alcohol and Smoking: Both substances can worsen mitochondrial function and should be avoided by people with MELAS.
- Annual Checkups: Regular medical appointments are crucial for monitoring various organ systems affected by MELAS, such as the heart, kidneys, eyes, and hearing, as well as checking for diabetes.
Research and the Future
Ongoing research into MELAS syndrome is focused on understanding the underlying mechanisms of mitochondrial dysfunction and developing targeted therapies to manage or potentially reverse the condition's symptoms.
- New Leads in Treatment: Recent studies have identified promising new treatment approaches for MELAS syndrome, including gene therapies aimed at addressing mitochondrial dysfunction at the molecular level. One such approach involves targeting the mitochondrial defects responsible for energy production deficits, which could potentially slow the progression of the disease. Researchers are also exploring the use of antioxidants and compounds that support mitochondrial function, with early results showing some promise in animal models.
- Drugs in Development: Various drugs are currently under investigation to help manage the symptoms of MELAS syndrome and improve quality of life. These treatments focus on enhancing mitochondrial function and addressing specific symptoms such as lactic acidosis and stroke-like episodes. Drugs in development are being tested for their ability to reduce oxidative stress, improve cellular energy production, and provide neuroprotective benefits. The aim is to offer patients better management options that could slow disease progression and improve outcomes.
To search for the best healthcare providers for Medical Genetics in Germany, India, Saudi Arabia, Singapore, Slovakia, Spain, Thailand, The UAE, The UK and The USA, please use our free Mya Care search engine.
To search for the best Neurology healthcare providers in Azerbaijan, Germany, India, Malaysia, Spain, Thailand, Turkey, UAE, UK and the USA, please use the Mya Care search engine.
To search for the best Doctors and Healthcare Providers worldwide, please use the Mya Care search engine.
Sources: