MELAS Syndrome

MELAS Syndrome

Description, Causes and Risk Factors:

MELAS syndrome is a group of disorders caused by mutations in mitochondrial genes (at least 9 have been identified) that alter transfer RNA molecules resulting in disruption of intramitochondrial synthesis of proteins involved in oxidative phosphorylation pathways. It is both clinically and genetically heterogeneous. One can expect that any familial occurrence would result from maternal transmission but the occurrence of heteroplasmy results in considerable variability in the severity of clinical disease.

The most commonly described gene mutation causing MELAS syndrome is a mitochondrial adenine-to-guanine transition at nucleotide pair 3243 (m.3243>G) encoding the mitochondrial tRNA. At least 29 other specific point mutations have been associated with the MELAS syndrome. These mutations lead to impaired oxidative phosphorylation, resulting in the inability to the mitochondria to produce sufficient ATP to meet the energy needs of the cell. This causes a shift to lactate production, which can be systemically noticed as lactate acidosis.

Due to variability in severity and symptoms and the problems confirming the diagnosis, the incidence of MELAS syndrome is difficult to assess. It is estimated to be as common as neuromuscular disease like Duchenne muscular dystrophy.

This progressive mitochondrial disorder primarily affects muscles and the CNS, including the visual system. The pattern of ocular deficits is not consistent and those that are present are not specific, requiring the clinician to take the entire neurological picture into consideration. Hemianopsia, cortical blindness and ophthalmoplegia may be present. The ERG can show reduced B-wave amplitudes and VEPs (visual evoke potential) may be absent. The optic nerve head has been described as normal without the atrophy often seen with other mitochondrial disorders. A pigmentary retinopathy may be seen.


The clinical picture is highly variable. Most commonly patients have myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. The onset of symptoms is usually in the first two decades of life, most commonly consisting of headaches of sudden onset accompanied by vomiting and seizures. The headaches may simulate migraines. Weakness, lethargy, and apathy may be present early. However, infants and young children may present with failure to thrive, developmental delay, and learning disabilities. Neurosensory deafness is often seen and peripheral neuropathy is usually evident. MRIs may show cerebellar hypoplasia and infarctions in the cerebral hemispheres. Some patients have calcifications in the basal ganglia. Patients may develop lactic acidosis. Muscle biopsies often show ragged, red fibers. The heart is commonly involved with both structural and rhythm defects. Depending upon the degree and location of brain damage, patients may have hemiparesis, lethargy, ataxia, myoclonic jerks, cognitive decline, and dementia. Morbidity and mortality are high.


Laboratory examination will show lactic acidosis in almost all patients. MRI of the brain in MELAS syndrome will typically show asymmetric lesions of the occipital and parietal lobes, mimicking ischemia, although not restricted to one specific vascular region.

ECG may demonstrate aspecific abnormalities suggestive of cardiomyopathy, like left ventricular hypertrophy, negative T-wave in the precordial leads, a left oriented electrical axis, and prolonged QTc.

Echocardiographic examination is mandatory in demonstrating cardiac involvement in mitochondrial disease. Next to left ventricular hypertrophy, diastolic and systolic dysfunction may be present.

Molecular diagnosis of mtDNA mutations is complicated by the variability in heteroplasmy depending on the specific tissue sampled. A detectable mutation in muscle cells is not necessarily detectable in leucocytes, cells regularly used for DNA analysis. Urine sediment cells and cheek mucosa appear to be a better alternative for DNA analysis.


No specific treatments are available for MELAS syndrome, although there are some suggestions that the use of 1-arginine and coenzyme Q10 in addition to vitamin supplementation might be advantageous. As in other cardiomyopathies, regular heart failure therapy is indicated, consisting of diuretics, ACE-inhibitors, and beta-blockers. In case of refractory heart failure despite optimal medical therapy, heart transplantation can be considered in selected patients. This requires extensive evaluation of extracardiac involvement especially with regard to potential contraindications such as recurrent strokes, dementia, and muscle waisting.

Furthermore, heart transplantation and other operations are generally accompanied by a significantly increased perioperative risk, in particular due to stroke, coma, seizures, respiratory failure, and cardiac arrhythmias. Perioperative management includes generous hydration, loading with intravenous glucose, and careful control of body temperature and pH.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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