How is the diagnosis made?
After a detailed interview (age of onset, symptoms, family history, etc.), the doctor performs a complete clinical examination, followed Par a request for one or more additional tests (based on blood tests, urine tests, radiological examinations, possibly a muscle biopsy, etc.). Their results guide genetic tests, which confirm the diagnosis of mitochondrial disease.
Types d’examens
Metabolic assessment
For what ?
Detect whether the patient’s cells are producing enough energy.
How ?
A blood sample is analyzed to measure certain key molecules (lactate, pyruvate, acetoacetate, and beta-hydroxybutyrate) that indicate dysfunction in energy production.
Imaging
For what ?
Check if abnormalities are visible in tissues and organs (brain, muscle, optic nerve, etc.) that need a lot of energy.
How ?
Brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can identify abnormalities in brain regions, such as cerebral lactate accumulation. Optical coherence tomography (OCT) provides detailed analysis of the retina and optic nerve.
Functional analyses of mitochondria
For what ?
To check whether the mitochondrial respiratory chain complexes are functioning correctly, and whether their interactions and/or assembly are correct.
How ?
By analyzing cells in a muscle or skin sample, the ability of these complexes to produce energy is measured. Values that are too low therefore indicate a deficiency in energy production.
Muscle tissue analysis
For what ?
To observe the impact of the disease on the muscles and how the mitochondria behave.
How ?
Muscle biopsy analysis can reveal whether mitochondria are arranged and functioning in an unusual way, and whether there are certain characteristics of muscle fibers that are specific to mitochondrial disease (appearance of red, ragged fibers).
Dosage of coenzyme Q10 (ubiquinone)
For what ?
Coenzyme Q10 is a key compound in mitochondria.
How ?
The level of this molecule is assessed in the blood or muscle. A low level can be a manifestation of the disease, sometimes treatable with supplements.
Genetic analyses
For what ?
Finding abnormalities in mitochondrial DNA or nuclear DNA from a sample of blood, urine, or tissue such as muscle. The presence of an abnormality already identified as deleterious (pathogenic variant) can confirm the diagnosis of mitochondrial disease.
How ?
By analyzing mitochondrial and then nuclear genes. Next Generation Sequencing (NGS) is now commonly used in diagnostic laboratories to simultaneously analyze a wide range of mitochondrial genes.
It is important to know that different sequencing technologies exist, which can consist of analyzing a gene, several genes in the form of panels, the entire mitochondrial genome or even nuclear genes (the 20,000 genes that make up the exome, or even the entire genome).
Please note
Identifying the mutation and the gene involved is important for genetic care and counseling, but also in view of the arrival of new treatments targeted at a particular mutation or gene. However, sometimes (in about half of cases) genetic analyses fail to identify the pathogenic variant, particularly because not all the genes involved in mitochondrial diseases are yet known.