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VERIFIED CONTENTAuthor: Katarzyna Wieczorek-Szukała, MD, PhD, medical biotechnologist, Medical University of Lodz

MELAS syndrome is a complex genetic disease that affects children and young adults. It manifests itself with progressive damage and the development of brain and muscle dysfunctions, headaches and a variety of neurological symptoms. The condition progresses inexorably, causing a disability in adolescence or early adulthood. Is it possible to treat MELAS syndrome? Where does this disease come from?

The nameof the MELAS syndromecontrary to appearances, it does not derive from the name of the discoverer of this disease. It is an acronym that describes a set of comorbid symptoms such as Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like Episodes; MELAS.

The disease is rare and is diagnosed in an average of 1 in 4000 people (at the same time it is considered one of the most common diseases with mitochondrial inheritance).

What is the cause of MELAS Syndrome?

MELAS syndrome is considered to be a mitochondrial hereditary genetic disease. Mitrochondrial inheritance means that both genders can be affected, but only women “pass on” related genes to future offspring. This is because the paternal mitochondria are present only in the neck of the male reproductive cell - the sperm (the so-called insert), located just in front of its tail.

During fertilization, only the head of the cell, which contains most of the genetic material, is involved in the formation of the zygote. The insert and tail are discarded, and with them the mitochodrial DNA (mtDNA).

All mitochondrial disorders, including those responsible for MELAS, are inherited from the mother. These types of genetic defects are the result of mutations that impair mitochondrial function, including the cycle of oxidative phosphorylation and energy production.

It has been found that the most common cause of the disease is a point mutation in the MTT1 mitochondrial gene (detected in up to 90% of cases). Other known mutations associated with this syndrome are also MTTQ, MTTH, MTTK and MTTS1.

Mitochondria are some kind of energy factories for the whole cellsof the body and regulate all functions and metabolism. Their defects are particularly acute in the functioning of the most active organs, including the brain and muscles. It is also suspected that the neurological symptoms of MELAS are caused by microdamages in the blood vessels (angiopathies) and nitric oxide deficiencies, which may result in impaired vasodilation in the brain.

Symptoms of MELAS Syndrome

Children with MELAS syndrome usually have normal early psychomotor development, and their he alth does not raise any concerns among medical specialists or parents. Symptoms usually only appear between the ages of 2 and 10. The onset of the disease is associated with:

  • growth deficiencies,
  • attacks of migraine headache,
  • progressive deafness,
  • anorexia,
  • fits and fits.

One of the characteristic features of this disease (which becomes visible during histopathological diagnostics and staining of the collected tissue) is the abnormal accumulation of mitochondria in the muscle fibers.

Dysfunctional mitochondria divide to try to compensate for poor energy production and appear bright red compared to the blue muscle fibers stained in the slide.

This image gives the impression of ragged red fibers (RRF). Muscle dysfunction (myopathy) in MELAS syndrome is initially manifested by exercise intolerance or weakening of the muscles of the trunk and upper limbs (the so-called proximal muscles).

As people age, attacks of neurological symptoms, known as "stroke-like episodes," appear more and more frequently. These incidents differ from a typical stroke (characteristic of the elderly) in that they do not fit into any vascular area.

Magnetic resonance imaging (MRI) images can be extremely variable and ambiguous, and the changes disappear faster than a typical stroke.

Neurological deficits are often focal and include:

  • hemiparesis (applies to the arm and leg on the same side of the body),
  • hemianopia (visual disturbances occurring in the middle of the field of view),
  • aphasia (difficulty speaking or understanding speech)
  • encephalopathy (chronic damage to brain structures),
  • epileptic seizures.

Such serious illnesses, especially in the period of growth and maturation of a young organism, translate into progressive impairment of motor functions, association and reasoning. Over time, vision and sensorineural defects may also worsenhearing loss.

Systemic changes in MELAS also affect other organ systems. Patients may also suffer from heart conduction disturbances, type II diabetes, kidney damage and chronic fatigue.

Diagnosis and treatment of the MELAS syndrome

Many specialists usually participate in the diagnosis of the MELAS Team: neurologists, cardiologists and ophthalmologists. For proper clinical evaluation, it is necessary to perform head imaging examinations, e.g. magnetic resonance imaging and computed tomography, and their careful evaluation.

In order to assess the structure of the tissue, muscle samples (in the form of a biopsy) and cerebrospinal fluid (lumbar puncture) are also taken for testing.

One of the blood test results confirming the presence of MELAS syndrome may also be elevated levels of lactic acid (lactic acidosis), which is associated with abnormal mitochondrial function. Lactate levels are also often elevated in the cerebrospinal fluid.

The final diagnosis of MELAS is based on the detection of specific mtDNA mutations. Of course, performing genetic tests earlier eliminates the need for other painful tests (e.g. muscle biopsy) - but it is very expensive.

Unfortunately, today there is no known method of treatment that would make it possible to stop the progression of the disease. Therapy is based on relieving symptoms, including antiepileptic drugs. Supportive, there are also supplements containing:

  • coenzyme Q10,
  • L-carnitine,
  • L-arginine.

They have been shown to help increase mitochondria's energy production, relieve severity of symptoms, and reduce the frequency of episodes.

Arginine is one of the precursors to the production of nitric oxide - thanks to which its administration can support the functioning of blood vessels and reduce the risk of stroke.

However, this does not change the fact that MELAS syndrome is a very serious disease leading to permanent disability, with a high risk of premature death.

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Category:

Genetic diseases