Questions & Answers

13. How do you diagnose mitochondrial disease?

Biochemical Tests

These tests involve taking samples of body fluids like blood, urine or Cerebrospinal Fluid (CSF) and are usually the first tests performed.

Elevated Lactate

Often (but not always), mitochondrial disease patients suffer from a condition known as lactic acidosis which is an increase in lactic acid concentration in the body.

It is common therefore to have the levels of lactate measured to see if these are abnormal. High levels of lactate, along with other symptoms, typically do indicate a mitochondrial problem, however blood lactate can also be seen after vigorous exercise or in other non-related conditions which can confuse things.

To complicate matters even more, elevated levels of lactate are not seen in all types of mitochondrial diseases which means that a normal result does not rule out a mitochondrial disorder.


Mitochondrial disease is most frequently caused by faulty proteins within the respiratory chain which reduce energy production so it is important to pinpoint the source of the problem.

Enzymology tests measure the activity of these proteins. The function of each of the five proteins of the respiratory chain is tested using biochemical reactions to identify exactly which proteins are faulty.

Amino Acids & Organic Acids

Urine can also be tested for levels of certain amino acids, proteins and organic acids which might indicate a mitochondrial disorder.

Histochemical Tests Biopsies

Doctors might also take a piece of tissue (biopsy) and examine the chemicals within it. This is usually a muscle biopsy as this is the easiest to obtain but occasionally liver or skin may be sampled depending on the symptoms of the disease.

This procedure is quite invasive, and will usually require a general anaesthetic in a child, which may not be advised. Results are usually not available for at least 6 weeks after the biopsy has been taken.

At this level of analysis, the appearance (histology) of the tissue is tested. Chemical staining may reveal abnormalities like 'ragged red fibres' which are abnormal mitochondria beneath the muscle membrane (although these are rarely seen in children under 5) or COX negative fibres indicating deficiency of cytochrome oxidase (COX). 

Ragged red fibres

Ragged Red Fibers

Although these can both be a characteristic of mitochondrial disease their absence doesn’t exclude mitochondrial disease as it may just be that the piece of tissue examined did not contain a sufficient number of the faulty mitochondria to detect a problem. In these cases doctors usually rely on looking at all the symptoms and what is the most likely diagnosis.

Neurological Evaluation 

Some types of mitochondrial disease show specific patterns of change on an MRI brain scan. Symmetrical lesions in the area known as the basal ganglia are common, as is atrophy (decrease in size) of certain areas.

MRS tests may show elevated levels of lactate in the brain.

Nerve conduction tests may be useful in diagnosing neuropathy, and Electromyography (EMG) can diagnose myopathy.

Cardiac Evaluation

Electrocardiography and echocardiography may reveal certain heart conditions such as a conduction disorders or cardiomyopathy.

Ophthalmological Testing (Visual)

Electroretinography is helpful for measuring optic nerve thickness and range of eye movements and may be helpful in diagnosing eye conditions such as retinitis pigmentosa.

Genetic Testing:

The ultimate goal in mitochondrial disease diagnosis is to find the exact genetic mistake, or mutation, responsible.

Next Generation Sequencing is able to determine the exact location of the mutation and the type of mutation it is (deletion, duplication, point mutation etc). A specific type of mutation at a specific location is often the identity for a mitochondrial disease and distinguishes it from other diseases that may have similar characteristics.

These techniques can give genetic diagnosis to many more families and look to be the way forward for diagnosing mitochondrial disorders.

At present this kind of genetic testing is not available on the NHS so The Lily Foundation are very proud to be able to fund this testing to give our families the answers they need.

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