Melas Syndrome
Disease Details
Family Health Simplified
- Description
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MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a rare genetic disorder that affects mitochondria, causing a range of symptoms including muscle weakness, neurological issues, and metabolic problems.
One-sentence description:
MELAS syndrome is a rare mitochondrial disorder characterized by muscle weakness, neurological deficits, and metabolic complications such as lactic acidosis. - Type
- MELAS syndrome is a mitochondrial disorder. It is transmitted through maternal inheritance, meaning it is passed down from mother to offspring via mitochondrial DNA.
- Signs And Symptoms
- 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. Children with MELAS often have normal early psychomotor development until the onset of symptoms between 2 and 10 years old. Though less common, infantile onset may occur and may present as failure to thrive, growth retardation and progressive deafness. Onset in older children typically presents as recurrent attacks of a migraine-like headache, anorexia, vomiting, and seizures. Children with MELAS are also frequently found to have short stature.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.
- Prognosis
- MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a progressive disorder with a variable prognosis. The severity and progression can differ greatly among individuals. Factors influencing prognosis include the age of onset, the degree of mitochondrial dysfunction, and the specific genetic mutation involved. In general, earlier onset and more severe symptoms are associated with a poorer prognosis. Regular monitoring and supportive treatments can help manage symptoms and improve quality of life.
- Onset
- MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) typically has an onset in childhood to early adulthood, generally between the ages of 2 and 15. However, it can sometimes present later in adulthood. The progression and severity of symptoms can vary widely among affected individuals.
- Prevalence
- The prevalence of MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is not precisely known but is estimated to be approximately 1 in 4,000 to 1 in 10,000 individuals.
- Epidemiology
- The exact incidence of MELAS is unknown. It is one of the more common conditions in a group known as mitochondrial diseases. Together, mitochondrial diseases occur in about 1 in 4,000 people.
- Intractability
- MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is currently considered intractable. There is no cure, and treatment focuses on managing symptoms and complications. The progressive nature of the disorder and its genetic basis contribute to its intractability.
- Disease Severity
- MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a progressive and severe condition. It impacts multiple organ systems, often leading to neurological deficits, muscle weakness, and metabolic complications. Severity varies among individuals, but the disease often significantly impairs quality of life and can reduce life expectancy.
- Healthcare Professionals
- Disease Ontology ID - DOID:3687
- Pathophysiology
- MELAS syndrome, or Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, is primarily caused by mutations in mitochondrial DNA (mtDNA), most commonly in the MT-TL1 gene. These mutations impair the function of mitochondria, crucial for energy production. The dysfunction leads to impaired ATP synthesis, increased production of reactive oxygen species, and the accumulation of lactic acid due to increased anaerobic metabolism. This mitochondrial dysfunction particularly affects high-energy-demand tissues such as the brain and muscles, causing a variety of neurological and muscular symptoms.
- Carrier Status
- MELAS syndrome, which stands for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, is a mitochondrial genetic disorder. It is typically caused by mutations in mitochondrial DNA, which is inherited maternally. Carrier status for mitochondrial diseases is not applicable in the traditional sense, as these conditions are passed from mother to child via mitochondria present in the egg cell. Therefore, carrier status is not relevant due to the non-Mendelian inheritance pattern of mitochondrial DNA.
- Mechanism
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MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is caused primarily by mutations in mitochondrial DNA (mtDNA). The most common mutation associated with MELAS is the A3243G mutation in the MT-TL1 gene, which encodes a mitochondrial tRNA for leucine.
**Mechanism:**
MELAS is characterized by defective mitochondrial function, which impairs cellular energy production. Mitochondria generate energy in the form of ATP through oxidative phosphorylation. In MELAS, mutations in mtDNA impair the function of the electron transport chain, reducing ATP production and leading to increased production of reactive oxygen species (ROS).
**Molecular Mechanisms:**
1. **tRNA Mutation:** The A3243G mutation in the MT-TL1 gene affects the structure and function of mitochondrial tRNA(Leu), essential for mitochondrial protein synthesis. This disruption impacts the translation of essential components of the electron transport chain.
2. **Electron Transport Chain Dysfunction:** Altered mitochondrial protein synthesis leads to deficiencies in complex I and IV of the electron transport chain, compromising ATP production and leading to a buildup of intermediary metabolites like pyruvate.
3. **Lactic Acidosis:** Impaired oxidative phosphorylation forces cells to rely heavily on anaerobic glycolysis, resulting in the overproduction of lactate, leading to lactic acidosis.
4. **Production of ROS:** Dysfunctional electron transport chains increase the leakage of electrons, leading to the overproduction of ROS, which can damage mitochondrial and cellular components further.
5. **Cellular and Tissue Damage:** Energy-deficient states and oxidative stress lead to degeneration of tissues, particularly in high-energy demanding organs like the brain and muscles, resulting in the characteristic symptoms of MELAS syndrome.
Understanding these mechanisms helps in exploring potential therapeutic approaches, which may include strategies to enhance mitochondrial function or reduce oxidative stress. - Treatment
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There is no curative treatment. The disease remains 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. Treatment for MELAS currently is 1. support the good mitochondria that is left with a mito cocktail and 2. avoid known mito toxins.
Also the following supplements may help:
CoQ10 has been helpful for some MELAS patients. B complex 100 is recommended as the B vitamins are the energy vitamins. 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. Citrulline is also used as citrulline makes the plasma arginine higher, these doses are being studied at Baylor. Treatment with IV arginine is thought to relax the blood vessels to the brain, via nitric oxide. https://jamanetwork.com/journals/jamaneurology/article-abstract/2499460 - Compassionate Use Treatment
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MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a genetic disorder affecting mitochondrial function. There is no definitive cure, but several treatments and interventions are considered under compassionate use or experimental status to manage and potentially alleviate symptoms. Here are some examples:
1. **Compassionate Use Treatments:**
- **Coenzyme Q10 (CoQ10):** May help improve mitochondrial function.
- **L-arginine and L-citrulline:** These amino acids may help reduce the frequency and severity of stroke-like episodes by improving blood flow.
2. **Off-label or Experimental Treatments:**
- **Idebenone:** A synthetic analog of CoQ10, currently under investigation for various mitochondrial disorders.
- **EPI-743 (Vincerinone):** An investigational drug that targets and supports mitochondrial function.
- **Gene Therapy:** Experimental approaches aimed at correcting the underlying genetic mutations causing the disease.
These treatments aim to manage symptoms and improve quality of life but have varying degrees of efficacy and are usually considered when conventional treatments provide insufficient relief. Always consult healthcare professionals for personalized medical advice and the latest treatment options. - Lifestyle Recommendations
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For MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes), lifestyle recommendations can help manage symptoms and improve quality of life:
1. **Balanced Diet**: Follow a nutrient-rich diet that supports mitochondrial function, including plenty of antioxidants from fruits and vegetables.
2. **Regular Exercise**: Engage in moderate, low-impact exercise to improve muscle strength and fatigue. Avoid overexertion, which can exacerbate symptoms.
3. **Stress Management**: Implement stress-reduction techniques such as yoga, meditation, or deep-breathing exercises.
4. **Regular Medical Check-ups**: Stay in close contact with healthcare providers for ongoing monitoring and to manage complications.
5. **Adequate Rest**: Ensure plenty of rest and sleep to help rejuvenate the body.
6. **Avoid Toxins**: Minimize exposure to substances that could further damage mitochondria, like tobacco smoke and excessive alcohol.
7. **Hydration**: Keep well-hydrated to support overall bodily functions.
8. **Genetic Counseling**: For affected individuals and family members considering having children, genetic counseling can provide important information and support.
It's always important to personalize these recommendations based on an individual's specific health status and needs. - Medication
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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome does not have a definitive cure. However, management focuses on alleviating symptoms and slowing disease progression. Medications used include:
1. **Coenzyme Q10**: May help improve mitochondrial function.
2. **L-Arginine**: Can be used during acute stroke-like episodes to improve blood flow and reduce symptoms.
3. **L-Citrulline**: Sometimes used to manage chronic symptoms by enhancing nitric oxide production.
4. **Antioxidants**: Such as vitamin E and vitamin C, to help reduce oxidative stress.
It is essential for treatment to be tailored to the individual, and regular follow-ups with a healthcare provider are crucial. - Repurposable Drugs
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MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a genetic disorder. Repurposable drugs that have been investigated include:
1. **Metformin** - Typically used for diabetes, it may help by reducing oxidative stress.
2. **Arginine and Citrulline** - Amino acids that can help manage stroke-like episodes.
3. **Coenzyme Q10** - A supplement that may support mitochondrial function.
4. **L-arginine** - Can help improve blood flow and manage symptoms.
These drugs are not definitive treatments but are being explored for their potential to alleviate symptoms and improve quality of life. Always consult with a healthcare provider for personalized medical advice. - Metabolites
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MELAS syndrome is a mitochondrial disorder that stands for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes.
Metabolites associated with MELAS syndrome often include elevated levels of lactate and pyruvate in the blood and cerebrospinal fluid. This elevation is due to impaired mitochondrial function, leading to poor oxidative phosphorylation and reliance on anaerobic metabolism.
"NAN" does not correlate with typically relevant terminology for MELAS syndrome. If you meant "None" or something else, please clarify or specify further. - Nutraceuticals
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For MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes), nutraceuticals are sometimes considered to manage symptoms and improve quality of life. Commonly used nutraceuticals include:
1. **Coenzyme Q10 (CoQ10)**: Supports mitochondrial function and energy production.
2. **L-Carnitine**: Enhances mitochondrial fatty acid metabolism and energy production.
3. **Alpha-Lipoic Acid**: Acts as an antioxidant and helps in mitochondrial energy metabolism.
4. **B Vitamins** (especially B1, B2, B3, B6, B7, B12, and folate): Support various aspects of mitochondrial metabolism and energy production.
These nutraceuticals are not cures but may help in managing the symptoms associated with MELAS syndrome. Always consult with a healthcare professional before starting any new supplement regimen. - Peptides
- MELAS syndrome is a mitochondrial disorder. There is interest in using certain peptides, such as elamipretide, to improve mitochondrial function in these patients. Elamipretide targets the inner mitochondrial membrane to enhance energy production. Research is ongoing to determine the effectiveness and safety of such treatments for MELAS syndrome.