MERRF Syndrome

MERRF syndrome (Myoclonic Epilepsy with Ragged-Red Fibers, myoclonus-epilepsy, "torn" red fibers) was first described in 1980. Later, the disease was allocated to an independent nosology.

[1], [2], [3]

Causes and pathogenesis of MERRF syndrome

The syndrome is caused by point mutations in the gene of lysine tRNA 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, it can be determined with other forms of damage to the nervous system (for example, in myoclonus-myopathy with lipomas).

[4], [5], [6], [7], [8]

Symptoms of MERRF Syndrome

The disease is characterized by pronounced clinical polymorphism, including familial, and has a progressive character. The age of the manifestation varies considerably from 3 to 65 years. The disease begins with increased fatigue during physical exertion, the appearance of pain in the calf muscles, reducing the processes of memorization and attention. In the expanded stage, myoclonus-epilepsy develops , including ataxia and dementia. Myoclonus is observed in 85% of cases. It manifests itself in the form of bilateral jerks, the number of which is quite variable. Epileptic myoclonus often correlates with EEG and EMG data. Then, ataxia and dementia join. Gait shakiness and violation of the coordination samples are also very variable. The sequence of clinical symptoms in the MERRF syndrome may change. Seizures are observed in almost 70% of patients, they are often tonic-clonic, 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. The myopathic syndrome is not very pronounced. To a lesser extent, other changes may develop: lactate acidosis (23%), optic atrophy (22%), sensory disturbances, peripheral neuropathies, decreased tendon reflexes, focal neurological symptoms, etc. A number of authors point to the key diagnostic signs: myoclonus- epilepsy, ataxia, dementia in combination with neurosensory deafness, violation of deep sensitivity and atrophy of the optic nerves.

The severity of the disease and the degree of progression differ in variety even within the same family.

Diagnosis of MERRF Syndrome

Diagnosis of MERRF syndrome is based on laboratory data (expressed lactate acidosis in the blood, increased levels of lactate and pyruvate in the cerebrospinal fluid, decreased activity of mitochondrial enzymes in muscle biopsies), EEG (basic activity disorganization, generalized "polyspike waves", diffuse slow waves by all leads and others), the results of brain MRI (diffuse brain atrophy, changes in white matter, sometimes calcification of basal ganglia). When examining muscle biopsies, typical "torn red fibers" are revealed.

The main criteria of the MERRF syndrome are:

• mitochondrial type of inheritance;
• wide age range of disease manifestation (3-65 years);
• combination of myoclonus, ataxia, dementia and neurosensory deafness, atrophy of the optic nerve and violations of deep sensitivity;
• progressing course of the disease;
• lactate acidosis;
• characteristic EEG changes ("polyspike-wave" complexes);
• characteristic morphological changes in muscles (biopsy specimens of skeletal muscles reveal "torn" red fibers).

Differential diagnosis is carried out with epileptic syndromes accompanied by myoclonias, as well as other mitochondrial diseases, in which there are individual symptoms that are part of the MERRF syndrome.

[9], [10], [11]

Treatment of MERRF syndrome

Treatment of MERRF syndrome is aimed at correction of energy metabolism disorders, decrease in the degree of lactate acidosis, prevention of damages of mitochondrial membranes by free oxygen radicals. For this purpose, appoint riboflavin, nicotinamide, cytochrome C, coenzyme Q-10, anticonvulsant drugs (derivatives of valproic acid, clonazepam, etc.).