MERRF syndrome

A rare mitochondrial disorder

MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibers) is a rare mitochondrial disorder that affects multiple systems in the body. It is characterized by myoclonus, epilepsy, ataxia, muscle weakness, and the presence of ragged red fibers in muscle biopsy.

Pathophysiology

Mitochondrial DNA

MERRF syndrome is caused by mutations in mitochondrial DNA (mtDNA), which is inherited maternally. The most common mutation associated with MERRF is the A8344G mutation in the mitochondrial tRNA^Lys gene. This mutation impairs mitochondrial protein synthesis, leading to defective oxidative phosphorylation and decreased ATP production. As a result, tissues with high energy demands, such as the brain and muscles, are particularly affected.

Clinical Features

The clinical presentation of MERRF syndrome is highly variable, but the hallmark features include:

• Myoclonus: Sudden, involuntary muscle jerks that are often the first symptom.
• Epilepsy: Seizures of various types, including generalized tonic-clonic seizures.
• Ataxia: Loss of coordination and balance, leading to difficulties with walking and fine motor skills.
• Muscle Weakness: Progressive weakness and fatigue, often accompanied by exercise intolerance.
• Ragged Red Fibers: Abnormal muscle fibers that appear ragged and red when stained and viewed under a microscope.

Ragged red fibers in muscle biopsy

Other symptoms may include hearing loss, short stature, cardiomyopathy, and peripheral neuropathy. The severity and progression of symptoms can vary widely among individuals.

Diagnosis

Diagnosis of MERRF syndrome is based on clinical evaluation, family history, and genetic testing. Muscle biopsy showing ragged red fibers is a key diagnostic feature. Genetic testing can confirm the presence of mtDNA mutations associated with MERRF.

Management

There is currently no cure for MERRF syndrome, and treatment is primarily supportive and symptomatic. Management strategies may include:

• Antiepileptic drugs to control seizures.
• Physical therapy to improve mobility and coordination.
• Occupational therapy to assist with daily activities.
• Hearing aids for those with hearing loss.

Prognosis

The prognosis for individuals with MERRF syndrome varies depending on the severity of symptoms and the specific mtDNA mutation. Some individuals may experience a relatively mild course, while others may have significant disability and reduced life expectancy.

Related pages

• Mitochondrial disease
• Mitochondrial DNA
• Epilepsy
• Ataxia