MERTK

MELAS Syndrome

MELAS syndrome is a rare genetic disorder that affects multiple systems in the body, particularly the nervous system and muscles. The acronym MELAS stands for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes. This condition is part of a group of disorders known as mitochondrial diseases, which are caused by mutations in the mitochondrial DNA (mtDNA).

Overview

MELAS syndrome is characterized by a variety of symptoms that typically begin in childhood or early adulthood. The most common features include muscle weakness, recurrent headaches, loss of appetite, vomiting, and seizures. A hallmark of MELAS is the occurrence of stroke-like episodes, which can lead to temporary muscle weakness or paralysis on one side of the body (hemiparesis), altered consciousness, and vision abnormalities.

Genetics

MELAS is caused by mutations in the mitochondrial DNA, which is inherited maternally. The most common mutation associated with MELAS is the A3243G mutation in the MT-TL1 gene, which encodes for mitochondrial tRNA for leucine. This mutation impairs the normal function of mitochondria, leading to decreased energy production and increased production of lactic acid.

Pathophysiology

The pathophysiology of MELAS involves impaired oxidative phosphorylation due to defective mitochondrial function. This results in decreased ATP production and increased anaerobic metabolism, leading to lactic acidosis. The energy deficit particularly affects high-energy-demand tissues such as the brain and muscles, contributing to the neurological and muscular symptoms observed in MELAS.

Clinical Features

- Stroke-like episodes: These episodes can mimic strokes but do not follow vascular territories. They can cause transient neurological deficits and are often associated with headaches and seizures. - Lactic acidosis: Elevated levels of lactic acid in the blood can lead to metabolic acidosis, contributing to fatigue and muscle weakness. - Myopathy: Muscle weakness and exercise intolerance are common due to impaired energy production. - Neurological symptoms: These include seizures, dementia, and hearing loss.

Diagnosis

Diagnosis of MELAS is based on clinical presentation, family history, and genetic testing. Muscle biopsy may show ragged red fibers, a characteristic finding in mitochondrial myopathies. Elevated lactate levels in blood and cerebrospinal fluid can also support the diagnosis.

Management

There is currently no cure for MELAS, and treatment is primarily supportive. Management strategies include: - Anticonvulsants: To control seizures. - Cochlear implants: For hearing loss. - Nutritional supplements: Such as coenzyme Q10, L-carnitine, and B vitamins, which may help improve mitochondrial function. - Physical therapy: To maintain muscle strength and function.

Prognosis

The prognosis for individuals with MELAS varies widely. Some may experience a relatively stable course, while others may have progressive neurological decline. Early diagnosis and supportive care can improve quality of life and outcomes.

Also see

- Mitochondrial disease - Leigh syndrome - Mitochondrial DNA - Genetic disorders