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Petri Dishes

Mitochondrial Diseases

Symptoms and Diagnosis

סמנים ואבחון

When do suspicions arise that one’s child is ill with a mitochondrial disease? Can pediatricians identify them and refer us to a specialist? 

Family doctors and pediatricians, to whom parents turn when the child is not developing well or is experiencing a certain disorder, are not always sufficiently aware of mitochondrial diseases, and sometimes parents aren’t referred soon enough to a specialist and the start of the treatment is delayed. When a child is referred to a child development institute or a pediatric neurologist, these specialists are aware of these diseases and are able to identify them by symptoms like muscular hypotonia, a sudden strabismus, inappropriate development and others. Medical geneticists as well as genetic counselors know and can identify signs that might indicate the presence of a mitochondrial disease.

The suspicion arises when the child has a neurological illness with symptoms involving a number of systems, for example, when there is an equilibrium disorder in a hepatic illness, or when neurological symptoms arise from different areas of the brain, like an eye-movement disorder or a movement disorder called dystonia. When there is a sudden loss of equilibrium with neurological or other systemic signs, especially during a feverish illness, this may indicate that the child has a mitochondrial disease.


Which diagnostic tests are carried out?

Survey testing is carried out through blood and urine tests.

Blood test for lactic acid - The body produces lactic acid when there is a defect in the aerobic production of energy. The body in fact tries to “by-pass” the defect in the mitochondrial respiratory chain, and by producing lactic acid provides itself with “fuel” from a different source. In children and adults who have a mitochondrial disease, the aerobic metabolism is defective, and muscular aches can occur (similar to those experienced by athletes after physical exertion).

Urine test for organic acids – Inappropriate levels are typical of a mitochondrial disease and can indicate its presence.

Blood test for amino acids – A high level of different amino acids in the blood can indicate the presence of a mitochondrial disease.

Blood test for carnitine – A low ratio of carnitine has been found in children with a mitochondrial disease.

MRI test – Its objective is to check for changes in the brain that are typical of mitochondrial diseases.

Nowadays (2019) it is customary in certain cases, where the presence of a specific mitochondrial disease, or a maternally inherited disease is suspected, to carry out different genetic testing in the early stages of the diagnostic process: testing for a specific common mutation(s) in a specific gene, or testing for a specific gene’s sequence in the nuclear or mitochondrial DNA (this is usually covered by the health services when the signs and symptoms are appropriate).

Panel testing of a number of genes, or a complete mitochondrial DNA sequencing (Both of these tests are not covered as yet by the health services).

Exome sequencing – This is as yet covered to a certain extent by a pilot study of the Health Ministry, with very specific criteria and when the disease has certain symptoms.


What are the treatment methods?

Nowadays (2019) in general there are no curative medicines or treatments for a primary mitochondrial disease. One objective is to give nutritional supplements such as vitamins K, C, Coenzyme-Q and others, in order to neutralize free radicals. This treatment is given as an attempt to improve the functioning of certain enzymes, prevent additional damage and maintain the present functional state.

The treatment through nutrition and vitamins does not alleviate the symptoms. Its objective is to try and maintain the respiratory chain and prevent secondary damage by free radicals, which are a by-product of the mitochondria’s inefficient functioning.

LHON disease – it is customary to administer large doses of the antioxidant IDEBENONE in the early phase of the disease and within not more than three months after the beginning of the loss of vision, in order to the stop the optic neuropathy, and in some cases reverse it.

There is a small number of mitochondrial diseases in which nowadays (2019) a specific experimental medical treatment is given within the framework of clinical trials and/or after receiving approval by the Helsinki Committee.

LEIGH disease –treatment with the medication EP300

Diseases that are caused by a deficiency of nucleotides due to an enzymatic defect, for example, TK2 def. – nucleotides are administered as a medication. Here too the treatment, as far as we know, is effective only in the early stages of the disease.

Life expectancy is different in every disease. In the LEIGH syndrome life expectancy is usually short. Death occurs in the first years due to respiratory arrest as a consequence of damage to the respiratory center in the brain stem.


Which prenatal (during pregnancy) diagnostic tests for mitochondrial diseases are carried out nowadays?

If a mutation in a nuclear-DNA gene, which causes a primary mitochondrial disease, has been already diagnosed, a prenatal and pre-implantation diagnosis can be done, as is the case with any other hereditary diseases. When the mutation is in an encoded gene in the mitochondrial DNA, which causes the disease and is maternally inherited, a prenatal diagnosis can be done, and a definite risk of recurrence can be given only in a small number of cases, in which it is known that the percentage of the existing mutation does not change during the pregnancy. A pre-implantation diagnosis cannot be done. Another possibility which exists in a small number of centers around the world (and involves a high cost), is an IVF which includes changing the embryo’s mitochondrial genetic material by implanting the embryo’s nucleus in the embryo of a donor whose mitochondrial DNA is normal.



Typical clinical manifestations in mitochondrial diseases:


Stroke in a young person


Optic neuropathy


Fatigability and exercise intolerance

Elevated levels of cerebrospinal fluid protein

Sensory hearing loss



Peripheral neuropathy

Vascular headache



Basal ganglia calcification

Written by Prof. Tally Lerman-Sagie, Head of Pediatric Neurology and Metabolic Diseases – Wolfson Medical Center (translated by Eric Bymel)

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