MERRF syndrome

MERRF syndrome (Myoclonic Epilepsy with Ragged-Red Fibers) was first described in 1980. Subsequently, the disease was identified as an independent nosology.

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Causes and pathogenesis of MERRF syndrome

The syndrome is caused by point mutations in the lysine tRNA gene at locus 8344 and 8356. As a result of mutation 8344, aminoacylation of tRNA decreases to 35-50%, its content decreases and premature termination of translation on mitochondrial ribosomes occurs. This mutation is non-specific and can be detected in other forms of nervous system damage (for example, in myoclonus myopathy with lipomas).

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Symptoms of MERRF syndrome

The disease is characterized by pronounced clinical polymorphism, including familial, and is progressive. The age of manifestation varies significantly from 3 to 65 years. The disease begins with increased fatigue during physical exertion, pain in the calf muscles, and decreased memory and attention processes. In the advanced stage, myoclonus epilepsy develops, including ataxia and dementia. Myoclonus is observed in 85% of cases. It manifests itself as bilateral twitching, the number of which is quite variable. Epileptic myoclonus often correlates with EEG and EMG data. Then ataxia and dementia join in. Unsteadiness of gait and impaired performance of coordination tests are also characterized by wide variability. The sequence of clinical symptoms in MERRF syndrome may change. Convulsions are observed in almost 70% of patients, they are often tonic-clonic in nature, but partial epileptic paroxysms may develop. Sensorineural hearing loss occurs in 50% of patients. It is caused by damage to the peripheral part of the auditory analyzer. Myopathic syndrome is expressed slightly. Other changes may develop to a lesser extent: lactic acidosis (23%), optic nerve atrophy (22%), sensory impairment, peripheral neuropathy, decreased tendon reflexes, focal neurological symptoms, etc. A number of authors point to key diagnostic signs: myoclonus epilepsy, ataxia, dementia combined with sensorineural deafness, impaired deep sensitivity and optic nerve atrophy.

The severity of the disease and the degree of progression vary widely even within the same family.

Diagnosis of MERRF syndrome

The diagnosis of MERRF syndrome is based on laboratory data (pronounced lactic acidosis in the blood, increased levels of lactate and pyruvate in the cerebrospinal fluid, decreased activity of mitochondrial enzymes in muscle biopsies), EEG (disorganization of basic activity, generalized "polyspike waves", diffuse slow waves in all leads, etc.), and MRI of the brain (diffuse brain atrophy, changes in white matter, sometimes calcification of the basal ganglia). Muscle biopsies reveal typical "ragged red fibers".

The main criteria for MERRF syndrome are:

• mitochondrial type of inheritance;
• wide age range of disease manifestation (3-65 years);
• a combination of symptoms of myoclonus, ataxia, dementia and sensorineural deafness, optic nerve atrophy and deep sensory disturbances;
• progressive course of the disease;
• lactic acidosis;
• characteristic EEG changes (polyspike-wave complexes);
• characteristic morphological changes in muscles (in biopsies of skeletal muscles, “torn” red fibers are revealed).

Differential diagnosis is carried out with epileptic syndromes accompanied by myoclonus, as well as other mitochondrial diseases, in which individual symptoms included in the MERRF syndrome are encountered.

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Treatment of MERRF syndrome

Treatment of MERRF syndrome is aimed at correcting energy metabolism disorders, reducing the degree of lactic acidosis, and preventing damage to mitochondrial membranes by free oxygen radicals. For this purpose, riboflavin, nicotinamide, cytochrome C, coenzyme Q-10, and anticonvulsants (valproic acid derivatives, clonazepam, etc.) are prescribed.