What is the Mitochondria?
It is an organelle with small circular DNA and ribosomes, located in the cytoplasm of cells, responsible for energy production in the cell and where oxygenated respiration takes place. It is surrounded by two membranes and is the place where Krebs cycle and oxidative phosphorylation events take place and ultimately ATP is formed, ie cell energy is produced.
It is a clinically heterogeneous group of diseases that occur as a result of dysfunction of the mitochondrial respiratory chain.
It may result from mutation of genes encoded by nuclear DNA or mitochondrial DNA (mtDNA).
Nuclear DNA 1500 genes and mitochondrial DNA 37 genes are responsible for the development of mitochondrial diseases.
While some mitochondrial disorders only affect a single organ (for example, the eye found in Leber’s hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with pronounced neurological and myopathic features.
Mitochondrial disorders can occur at any age. In many individuals with MtDNA mutations, Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with irregular red fibers (MERRF) It causes many syndromes such as neurological weakness (NARP) associated with pigmentosa or Leigh syndrome (LS).
Common clinical features of mitochondrial disease, whether involving a mitochondrial or nuclear gene, ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy and diabetes mellitus, diffuse central nervous system manifestations fluctuating epilepsy include dementia, migraine, stroke-like attacks, ataxia, and spasticity.
The high rate of fetal loss in mid and late pregnancy is a common condition that is often not noticed.
In some individuals, the clinical picture is seen as a feature of a particular mitochondrial disorder (eg, LHON, NARP, or maternal hereditary LS), and diagnosis is confirmed by identifying an mtDNA mutation in molecular genetic testing. However, it is not easy to diagnose in many individuals and a more detailed approach is needed, including family history, blood and / or CSF lactate concentration, neurological imaging methods, cardiac evaluation, and molecular genetic testing for an mtDNA or nuclear gene mutation.
As molecular genetic tests to make a diagnosis in an individual; Sequence analysis of single genes, multi-gene panel test, whole exome or whole genome analysis as well as whole mitochondrial genome analysis are performed.
Mitochondrial Genome Analysis is like searching for an address in a city. While searching for an address in a city, it can be compared to searching for houses that live near electrical transformers that provide the city’s energy and illuminate the city. Since we liken the streets to genes, a transformer district consisting of approximately 37 streets (mitochondrial genes) is investigated. More broadly, as 1500 genes cause mitochondrial disease, the city should also be sought in homes close to small transformers consisting of 1500 streets.
In our center, there is a “37 amplitude package” that we call “CentoMiTO”, as well as a “Comprehensive Mitochondrial Diseases package” containing 37 genes and 1500 genes. Analysis is carried out in CENTOGENE laboratories, which is one of the leading laboratories of Europe and the world on rare diseases and is headquartered in Germany, and test results and clinical reporting are made using CentoMD, one of the largest mutation databases in the world.
Patients applying to our center; A detailed report containing detailed clinical information, all previous tests and family tree is prepared, after giving detailed information about the tests, the consent documents are signed, and then all the information is entered into the CENTOPORTAL system by processing the blood samples taken on special cards. The samples taken are shipped to Germany on the same day with special cards and the results are obtained in about a month.
After the results are obtained, detailed interpretation of the results is made and genetic counseling is given. In addition, after discussing the clinical and molecular aspects of the patient, the patient’s diagnosis becomes clear and the treatment method is determined more clearly by the physician.