MERRF Syndrome

At a glance

MERRF is an acronym that stands for Myoclonus Epilepsy Ragged-Red Fibers. It is part of a larger spectrum of muscular disorders called mitochondrial encephalomyopathies. The most frequent symptom is myoclonic seizures that are usually sudden, brief, jerking spasms that can affect the limbs or the entire body. Ataxia, lactic acidosis, dysarthria, optic nerve atrophy, short stature, hearing loss, dementia, and nystagmus may occur. Progressive peripheral neuropathy causes altered sensation that reproduces walking on pins-and-needles. Most patients have signs of cardiomyopathy and dysrhythmia, usually Wolff-Parkinson-White Syndrome. Occasionally, patients may show lipomas around the neck and retinitis pigmentosa.

Synonyms

Fukuhara Syndrome; Myoclonus Epilepsy Ragged Red Fibers Syndrome; Myoencephalopathy Ragged-Red Fiber Disease Syndrome.

Incidence

MERRF Syndrome is a rare disorder and the exact incidence remains unknown. It affects males and females equally. The estimated prevalence is established at 1:400,000 in Northern Europe. However, most believe that mitochondrial myopathies are possibly unrecognized or underdiagnosed in the general population which makes it difficult to determine the true prevalence of the disease.

Genetic inheritance

Mitochondrial; incidence of affected children is dependent upon maternal mutant load.

Pathophysiology

Defect of the respiratory chain enzymes, mainly complexes I and IV.

Diagnosis

Clinical and laboratory confirmation of elevated pyruvate and lactate. Muscular biopsy shows ragged-red muscle fibers, and the biochemical defect is often segmental on histochemistry.

Clinical aspects

Clinical spectrum is proportional to the amount of normal and mutant DNA. Onset is in the neonatal period, with mental deterioration, intention tremor, myoclonic epilepsy, spasticity, ataxia, muscle weakness and atrophy, myopathy, and sensory neural hearing loss. The neuropathologic findings are (a) degeneration of dentate nucleus, red nucleus, globus pallidus, subthalamic nucleus, and pontine tegmentum; (b) degeneration of the Clarke column (the dorsal nucleus of the spinal cord), spinocerebellar tract, posterior column and corticospinal tract, and posterior spinal nerve root and sural nerve; and (c) degeneration of substantia nigra, locus coeruleus, cerebellar cortex, and inferior olivary nucleus.

Precautions before anesthesia

Diagnosis of mitochondrial disease should be considered in any child with a multisystem neurologic disorder or who is being investigated for hypotonia. Anesthesia-related morbidity and mortality risk is essentially linked to the preoperative status of the child, that is, the number and extent of organ dysfunction. The presence of a mitochondrial disease is not considered a risk for malignant hyperthermia. Avoid any elective anesthesia/surgery in the presence of infection or temperature because cytokines (mainly tumor necrosis factor [TNF]), inhibit some complex of the respiratory chain. The following should be checked: central nervous system (seizures, myoclonus, strokes, swallowing problems); metabolic (usual venous or arterial concentration of lactates and glucose); muscles...