Mitochondria are small complex structures, which exist in every cell of the body (except red blood cells) and produce most of the energy which we need to grow and live. The organs on the body which require a lot of energy to work properly are particularly dependent on well functioning mitochondria (brain, heart, skeletal muscle, kidney, endocrine glands and bone marrow), and these are the organ systems most commonly affected in mitochondrial diseases.

There are from one to several hundred mitochondria in each cell and each contains the complex molecules necessary to carry out our energy making chemical reactions as well as other functions necessary for cell metabolism. The energy pathways are the most important and allow us to break down carbohydrate, fat and oxygen to live. Electrons from these food molecules are passed down a series of complex molecules called the electron transport chain. The final molecule in the chain, cytochrome oxidase, passes the electrons to oxygen molecules.

When enough mitochondria are not working correctly a disease may develop and often involve the brain because of the tremendous energy requirement of the brain cells. Mitochondrial diseases are very variable in their features, so called clinical heterogeneity. The variability results from the fact that different organ streams contain different amounts of diseased mitochondria and those tissues with a high percentage of diseased mitochondria will be functionally impaired. The diseases are whole body diseases but the exact features of the disease will vary from one patient to another. Some will have a predominately brain or nerve disease whilst others will have muscle disease (mitochondrial myopathy), cardiac disease (cardiomyopathies), endocrine, renal or bone marrow disease or a mixture. Many mitochondrial diseases result in the accumulation of organic acids in the body. These are usually normal metabolic intermediates but when present in excess, the acidosis itself may be damaging or even life-threatening. Lactic acid accumulation is a common problem.

Treatments are not very effective however some effects of the diseases can be treated such as cardiac arrhythmia, seizure disorders, renal bicarbonate loss and hypoglycaemia. As there is no convincing evidence to date of any clear benefit of drug therapies in most archetypal mitochondrial disorders or those neurodegenerative conditions with evidence of mitochondria dysfunction, attention has turned to the development of genetic therapies and the possibility of Neuro protection. New horizons and hopes may lie with genetic strategies. Techniques for manipulating the mitochondrial genome are being investigted as this cure result in a one-off treatment or cure whereas nuclear manipulation would necessitate treatment for life.

Inheritance Patterns:   Some mitochondrial diseases are clearly inherited and those involving mitochondrial DNA may be inherited through the maternal side as almost all mitochondria comes from the mother. Most inherited mitochondrial diseases however are so called nuclear DNA defects with inheritance from wither the mother or father, or in most cases both. This latter inheritance pattern is called autosomal recessive and in this case the risk of reoccurrence in a sibling is 25% or 1 in 4. Most childhood onset mitochondrial diseases are inherited although in some cases the affected child seems to be the only affected family member.

Diseases resulting from mitochondrial deletions of large parts of the DNA mitochondrial molecule are usually sporadic without affecting other family members. Genetic counselling is complex for mitochondrial diseases.

Pre-Natal Diagnosis: Is only available for a few disorders

Further information available from:

The Children's Mitochondrial Disease Network (EMDN)
Mayfield house
30 Heber Walk, Chester Way,
Northwich
Cheshire CW9 5JB
(Tel Helpline and Fax: 01606 44733)

Web: www.emdn-mitonet.co.uk

e-mail: paul.preston@emdn-mitonet.co.uk

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