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At a glance

MELAS is an acronym that stands for Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke. It is a progressive neurodegenerative disorder that is part of a family of mitochondrial cytopathies that includes MERRF and Leber’s Hereditary Optic Neuropathy (see Other conditions to be considered below). It is characterized by early symptoms of generalized seizures, recurrent headaches, loss of appetite, and recurrent vomiting. Stroke-like episodes with temporary hemiparesis muscle weakness may also occur, affecting consciousness, vision, hearing, motor skills, and intellectual functions. Other clinical features include diabetes mellitus, deafness, episodic vomiting, seizures, and cortical blindness.

Synonyms

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, Stroke-Like Episode Syndrome; Myopathy, Mitochondrial-Encephalopathy-Lactic Acidosis-Stroke Syndrome.

History

It was first characterized under this name in 1984.

Incidence

In the US adult population, the frequency is approximately 16.3:100,000. Internationally, the prevalence is approximately 10.2:100,000 in the Finnish population. It affects males and females between the ages of 4 and 15 years in equal numbers.

Genetic inheritance

Mitochondrial; the incidence of affected children is dependent upon maternal mutant load. It is a large heterogeneic syndrome with possible mutation of many genes such as MTTL1, MTND6, and MTTQs.

Pathophysiology

Multiple organ systems involved are the central nervous system, skeletal muscle, eye, cardiac muscle, and, more rarely, the gastrointestinal system. Approximately 80% of patients with the clinical characteristics of MELAS have a heteroplasmic A-to-G point mutation in the dihydrouridine loop of the tRNALeu (UUR) gene at base pair 3243 (ie, A3243G mutation). Mitochondrial angiopathy of a small vessel is responsible for contrast enhancement of affected regions and mitochondrial abnormalities of endothelial cells and smooth muscle cells of blood vessels. The multisystem dysfunction may be a result of both parenchymal and vascular oxidative phosphorylation defects. The effect of potent vasodilators (eg, nitric oxide) may be offset by increased production of free radicals in association with an oxidative phosphorylation defect leading to vasoconstriction. Defect of the respiratory chain enzymes, mainly the reduced form of nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase (complex I).

Diagnosis

Usually based on clinical criteria; lactate levels are elevated at rest and increase further with minimal exercise. The demonstration of ragged-red fibers on muscle biopsy is pathognomonic of the disorder. Electronic microscopy may show abnormal mitochondria and mitochondrial DNA (mtDNA) testing (80% have a mutation at base 3243 and 10% at base 3271). The stroke-like episodes usually are associated with infarcts exhibited on head CT scan or MRI. These infarcts have been hypothesized to be nonvascular and caused by transient oxidative phosphorylation dysfunction within the brain parenchyma.

Clinical aspects

These children have normal early development. Onset is most often during the second decade but can be seen as early ...

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