- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: 3/18/2025
Years published: 1993, 1998, 1999, 2000, 2001, 2011, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Fernando Scaglia, MD, FACMG, Associate Professor, Department of Molecular and Human Genetics, Baylor College of Medicine, for assistance in the preparation of this report.
Advertisement
Summary
MELAS syndrome or MELAS (short for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare genetic disorder that affects multiple systems in the body. It is caused by changes (variants) in mitochondrial DNA which provide energy for cells. Mitochondria are tiny structures inside cells that produce energy.1
Encephalomyopathy is a combination of encephalopathy and myopathy, which are diseases of the brain and muscles, respectively. Lactic acidosis is a condition in which there is an excessive buildup of lactic acid in the blood leading to a drop in pH (acidity).
People with MELAS syndrome may have stroke-like episodes (sudden neurological problems that do not follow the usual pattern of a stroke), seizures, memory loss, dementia, muscle weakness and trouble with physical activity. They have normal development as young children but later develop learning difficulties, frequent headaches and vomiting, hearing loss, nerve damage that affects sensation (peripheral neuropathy) and short stature.1,2,3
Doctors use special brain scans (MRI) to check for stroke-like damage that doesn’t follow normal blood vessel patterns. Many patients also have high lactic acid levels in their blood and show specific muscle tissue changes under a microscope known as “ragged red fibers.” 1
Most cases of MELAS are caused by changes (variants) in the MT-TL1 gene, which accounts for about 80% of cases. Other mitochondrial genes can also cause the condition, though less frequently.1,4,5,6
Mitochondrial DNA is inherited only from the mother. This means if a mother carries the variant, she can pass it on to her children. However, the severity of symptoms can vary greatly, even within the same family.
Treatment is directed to the specific symptoms that the affected person has.
MELAS affects multiple organs and can appear at any age, though most people develop symptoms before age 20. The condition gets worse over time and the symptoms can vary widely among individuals.1 Children with MELAS usually experience normal early psychomotor development until symptoms emerge between the ages of 2 and 15. Although less frequent, infantile- and adult-onset are possible. The earliest signs in babies may include developmental delay, where a child may take longer than expected to reach milestones like sitting, walking, or talking and they may have trouble gaining weight and growing at a normal rate (failure to thrive).5
MELAS signs and symptoms may include:1,2
The common radiologic features of MELAS include CT findings of basal ganglia calcification, a condition where calcium deposits build up in the basal ganglia, a part of the brain responsible for controlling movement, loss of brain tissue (atrophy) and multiple infarcts.5
The course of MELAS varies between individuals, but it generally worsens over time due to repeated stroke-like episodes and progressive neurological decline. Many affected people experience increasing disability, cognitive decline and muscle weakness as they age.1,5,6
MELAS is caused by changes (variants) in the mitochondrial DNA (mtDNA). Several genes can be affected, but the most common variant occurs in the MT-TL1 gene, specifically a change called m.3243A>G. Variants in other genes that can cause MELAS include MT-TQ, MT-TH, MTTK, MTTC, MTTS1, MTND1, MTND5, MTND6, and MTTS2.1,3,4,6,7
Mitochondria are the cell structures that carry the body’s instructions for regulating energy production. Genes for mitochondria (mtDNA) are inherited from the mother. This is because the mtDNA in sperm cells is usually lost during fertilization. A mother with a gene variant in mtDNA will pass the variant to all her children, and her daughters will pass the variant to their children.
Normal mitochondrial genes and gene variants can exist in the same cell, a situation known as heteroplasmy. The number of mitochondria with the gene variant may be outnumbered by the number of mitochondria with a normal gene. Symptoms may not appear until a significant proportion of mitochondria have mtDNA with the gene variant. The uneven distribution of normal genes and gene variants in mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of different symptoms in affected family members.6
Also, different organs require different amounts of energy. The brain and muscles, which need a lot of energy, are more likely to be affected. This explains why MELAS mainly causes neurological and muscle-related symptoms.1
Additionally, MELAS is influenced by interactions between mitochondrial DNA and regular (nuclear) DNA, which can make the condition more complex and variable from person to person.1,6
Mitochondrial diseases affect an estimated 1 in 5,000 people, with MELAS having an estimated prevalence of 1 in 4,000.6
MELAS is diagnosed based on symptoms, laboratory tests and genetic testing.1,6,7
The diagnosis is suspected based on the following signs and symptoms:
Stroke-like episodes before age 40 (although cases of later onset are reported)
The diagnosis is confirmed when genetic testing identifies a variant in one of the mitochondrial genes linked to MELAS. The most common gene tested is MT-TL1.
Other tests that may be performed include:
Since stroke-like episodes in MELAS can look like regular strokes so an MRI scan is essential to tell them apart. In MELAS, the affected brain areas do not match typical stroke locations, especially in children and teens. This helps confirm the diagnosis and rule out other causes of sudden neurological symptoms.
High lactic acid levels in the blood are often one of the first signs of MELAS, especially during a stroke-like episode. Lactic acid builds up when the mitochondria (the energy factories of cells) are not working properly, which happens in MELAS. Lactic acid levels are measured to help distinguish MELAS from other conditions that can cause strokes such as:6
People with MELAS typically have: 6
In contrast, if lactic acid is high due to tissue damage (like in a regular stroke), the lactate-to-pyruvate ratio is also high, but oxygen levels tend to be low. This difference helps to confirm a diagnosis of MELAS.6
Treatment
There is no cure for MELAS so treatment focuses on managing symptoms and improving quality of life. It is important to have a team of specialists including neurologists, heart doctors (cardiologists), kidney doctors (nephrologists) and hormone specialists (endocrinologists) who should work together to develop a personalized treatment plan.
Treatments that may reduce symptoms and slow disease progression include:
In addition to vitamins, other more advanced therapies may help:
Because these treatments can have side effects they must be carefully monitored by doctors.
In addition, treatment may include:
Scientists are researching new treatments that could help people with MELAS in the future including:7
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/One in 10 Americans lives with rare disease, many of whom fight a daily battle to access the care and support they need. Your gift to the National Organization for Rare Disorders (NORD®) funds life-changing programs and helps us advance policies and research to ensure that everyone gets the care they need AND deserve.