How is it diagnosed?

To prove the existence of mitochondrial disease in a newly presenting patient is a bit like doing a jigsaw puzzle. The collection of pieces and putting them into place begins with the family doctor and progresses to the mitochondrial specialist. After considering the possibility of mitochondrial disease it’s then a matter of putting the pieces on the table and turning them up the right way to see them all together!
Mitochondrial disease is a multi-system illness, so a thorough history and examination of all the organs mentioned above can be done by a GP. General questions about fatigue, muscles, nerve problems, intellectual/mental issues, hearing, sight, bowel/heart/liver/kidney problems, or diabetes are a good place to start. A family history of similar illnesses or symptoms is important, especially if the illness was atypical (e.g., atypical MS) or a death was unexplained. Because mitochondrial disease is relatively ‘new’ it is unlikely that there will be a clear and distinct family history of the illness.

Basic investigations such as hearing tests, eye tests, blood tests, etc., can be done straight away. The next and more specialised investigations are best done by a mitochondrial specialist or a neurologist with knowledge of the illness, or in the case of children, a metabolic geneticist.

Individual systems/organs can then be tested more thoroughly along with non-specific mitochondrial function tests using blood, urine, hair, skin cells or tissue biopsies etc. Results from the classical muscle biopsy may be misleading so a number of different tissues are now being used as samples.

A fairly clear picture of the puzzle should now be emerging. If not, then a six-monthly or yearly review can reveal more pieces.

The FINAL piece of the jigsaw puzzle would be a positive genetic test. Unfortunately, due to 1,400 genes making up a single mitochondrion and our ability to test only one at a time, this is often unlikely, especially in the lesser known genetic mutations of mitochondrial disease. Mitochondrial disease can therefore become a clinical diagnosis (that is, a diagnosis based on symptoms and signs and basic investigations) in the hands of the right specialist.