Your condition in review What is MELAS?

Mitochondrial Encephalomyopathy, , and -like Episodes (more commonly known as MELAS syndrome), is a rare disorder that affects many of the body’s systems, particularly the brain and (encephalo-) and muscles ().

MELAS syndrome affects boys and MELAS may experience involuntary girls equally and all ethnic groups muscle spasms, impaired muscle equally. Onset of the condition coordination, hearing loss, heart Symptoms may generally occurs at a young age, with and kidney problems, diabetes, and not appear until the approximately 75 percent of cases hormonal imbalances. mutation affects a beginning before the age of 20 years The distinguishing feature in and most before age 40. MELAS syndrome is the recurrence of significant proportion Stroke-like episodes and stroke-like episodes. Migraines occur of mtDNA. characterise in the majority of affected individuals MELAS syndrome. Mitochondrial and are often severe during the acute cause muscular and stage of a stroke. Individuals with neurological problems. Most people MELAS may also have psychiatric Genetics of MELAS with MELAS also have a buildup of conditions such as depressive lactic acid in their bodies (a condition disorders, cognitive impairments, MELAS is caused by a defect in one called lactic acidosis). This increased anxiety disorder or personality of several mitochondrial genes. level of acidity in the blood can lead change. People with MELAS may Mitochondrial (mt) genes are found in to vomiting, abdominal pain, extreme also have episodes of confusion and the DNA of cellular structures called tiredness (fatigue), muscle weakness, hallucinations often due to a fever mitochondria, which convert the and difficulty breathing. and/or headache. energy from food into a form that Stroke-like episodes involve cells can use. The genes that are not Features of MELAS temporary muscle weakness working correctly can be in any of on one side of the body, altered these mitochondrial genes called MT- The typical features of MELAS consciousness, vision abnormalities, ND1, MT-ND5, MT-TH, MT-TL1, and MT- syndrome are ones that make seizures, and severe headaches TV. Both normal and mutated mtDNA up the name of the disorder i.e. resembling migraines. Repeated can exist in the same cell, which is a mitochondrial encephalomyopathy stroke-like episodes can progressively situation known as . (muscle problems), lactic acidosis, damage the brain, leading to vision Symptoms may not appear until and stroke-like episodes, with the loss, problems with movement, the mutation affects a significant main symptoms being headaches and a loss of intellectual function proportion of mtDNA. The uneven and seizures. Early symptoms of (e.g. dementia). If there is a history distribution of normal and mutant MELAS may include muscle weakness of developmental delays, learning mtDNA in different tissues can affect and pain, recurring headaches, loss disabilities or attention deficit different organs in members of of appetite, difficulty breathing, disorder then this is typically the same family. This can result in exercise intolerance and seizures. discovered before the first stroke a variety of symptoms in affected Less commonly, people with has been experienced. family members.

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Confirmation of the diagnosis usually requires molecular, genetic testing and a muscle or brain biopsy.

The clinical diagnosis of MELAS is based on the following features: • Stroke-like symptoms, typically before the age of 40 • with seizures and/or dementia Mitochondria are tiny structures located within nearly all cells of the body. They are the parts • Mitochondrial myopathy, of the cell that are primarily responsible for creating energy. They do this by generating evidenced by lactic acidosis adenosine triphosphate (ATP), which is the essential “fuel” that drives all of the body’s functions. For this reason, mitochondria are often described as the “powerhouse” of the cell. and/or ragged red fibers on muscle biopsy. To confirm the diagnosis, two of Mutations in the mtDNA gene MT- changes in mtDNA to their children. the following are also required: TL1 cause more than 80 percent of In most cases, people with MELAS • Normal early psychomotor all cases of MELAS. These mutations inherit an altered mitochondrial gene development impair the ability of mitochondria from their mother. Less commonly, to make proteins, use oxygen, and the disorder results from a new • Recurrent headache produce energy. Researchers have mutation in a mitochondrial gene • Recurrent vomiting not determined how changes in and occurs in people with no family mtDNA lead to the specific signs and history of MELAS which is now able symptoms of MELAS. They continue to to be passed on. Management investigate the effects of mitochondrial There is no known treatment for gene mutations in different tissues, Diagnosis of MELAS MELAS syndrome, however, patients particularly in the brain. are managed according to what Children can only inherit this The diagnosis of MELAS is usually areas of the body are affected at a disorder from their mother. This is determined by clinical examination. particular time. Sensorineural hearing because egg cells contribute the However, confirmation of the loss has been treated with cochlear mitochondria to the developing diagnosis usually requires molecular, implantations; Anti-convulsant drugs embryo, and sperm do not. The genetic testing and a muscle or brain are used to help prevent and control condition can appear in every biopsy. The muscle biopsy shows seizures associated with MELAS generation of a family and can affect characteristic ragged fibers for MELAS syndrome (it is important to note that both males and females, but fathers syndrome and a brain biopsy shows Valproic acid should not be used as do not pass traits associated with the stroke-like changes. an anticonvulsant);

The above diagram is sourced from: http://www.gohmd.org/mitochondrial-function.html InTouch magazine Winter 2016 | 25 Your condition in review | MELAS

Diabetes mellitus is managed also been used, however, consistent by dietary modification, oral success hasn’t been reported. Therapies are hypoglycemic agents or insulin Therapies are sometimes used to sometimes used therapy, Migraine headaches and increase energy production by the cardiac manifestations are treated mitochondria and slow down the to increase energy in the usual manner with pain effects of the condition. Coenzyme production by relief medication or preventive q10 and L-carnitine have been mitochondria and medications. The use of L-, beneficial in some patients. a dietry supplement, has been Individuals with MELAS should slow down the effects reported to improve the symptoms also receive standard childhood of the condition. of disease during the acute stroke- vaccinations such as the flu vaccine like episode. and pneumococcal vaccine. This is and have because feverish illnesses may make the condition worse. In general, for patients with mitochondrial myopathies, moderate treadmill International Neuromuscular Conference training may be beneficial for maintaining muscles strength Sydney and endurance. Genetic counselling is available to families who have had a diagnosis of MELAS. This service provides information, helps families FOR understand inheritance patterns BUILDING THE FUTURE and what this means in their family, neuromuscular conference as well as enabling people to make more informed family-planning Bringing together people living with a neuromuscular decisions. condition, world leading researchers and clinicians, allied health professionals, service providers, Agents to avoid: Mitochondrial representatives of the NDIS and industry to this toxins including: aminoglycoside unique two day conference. antibiotics, linezolid, cigarettes and alcohol; Valproic acid for seizure Date treatment; dichloroacetate (DCA) Fri 17 - Sat 18 June 2O16 due to increased risk for peripheral Venue neuropathy. Novotel, Sydney Olympic Park Pregnancy management: Affected or at-risk pregnant women should Registration and Programme information www.nmconference.org.au be monitored for diabetes mellitus and respiratory insufficiency. This may require therapeutic interventions. R

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