The Children’s Mitochondrial Disease Network
is the only parental and professional based registered organization Within
the UK specializing in the complexities of Mitochondrial and
What are Mitochondria?
Mitochondria are small complex
structures, which exist in every cell of the body (except red blood
cells). The mitochondrion has been called the ‘powerhouse’ of
the cell, as these tiny structures produce most of the energy, which
we all need to grow and live. Those organs in the body, which
require a lot of energy to work properly, are particularly dependent
on well functioning mitochondria. The most energy dependent organs
are the brain, heart, skeletal muscle, kidney, endocrine glands and
bone marrow and these are the organ systems commonly affected in
There are from one to several
hundred mitochondria in each cell and each mitochondrion contains
the complex molecules necessary to carry our energy making chemical
reactions. Mitochondria perform many functions necessary for cell
metabolism but the energy producing pathways are the most important.
These pathways 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
One unique feature of mitochondria
is that they have there own DNA molecules, mitochondrial DNA, which
carries the genes containing the genetic message for several
critical components of the electron transport chain.
What is a Mitochondrial Disease?
When enough mitochondria are not
working correctly a disease may result. Mitochondrial diseases often
involve the brain because of the tremendous energy requirements 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 systems contain different amounts of
diseased mitochondria and only those tissues with a high percentage
of diseased mitochondria will be functional impaired. Mitochondrial
diseases are whole body diseases but the exact features of the
disease vary from one patient to another. Some patients will have
predominately brain disease or nerve disease. Others will have
muscle disease (mitochondrial myopathy), cardiac disease (cardiomyopathies),
endocrine, renal or bone marrow disease or a mixture of these and or
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 in mitochondrial diseases.
We used to think of mitochondrial
diseases as rare childhood disorders. Recently it has been
discovered that many commoner disorders such as diabetes and
ischemic heart disease have, in some cases, a mitochondrial basis.
Also, diseases of aging such as Parkinson’s disease and Alzheimer’s
disease may result in part from mitochondrial failure (The role that
mitochondrial abnormalities play in the cause of these diseases
remains to be established). In fact, the aging process itself may be
due to a lifetime of damage to mitochondria through oxidative stress
and accumulated damage to mitochondrial proteins and mitochondrial
Genetics of Mitochondrial
Some mitochondrial diseases are
clearly inherited and those involving mitochondrial DNA may be
inherited through the maternal side of the family as almost all
mitochondria come from the mother. Most inherited mitochondrial
diseases however are so called nuclear DNA defects with inheritance
from either the mother or father, or in most cases both. This latter
inheritance pattern is termed autosomal recessive and in this case
the risk of reoccurrence in a sibling is 25% or one in 1 in 4. Most
childhood onset mitochondrial diseases are inherited although in
some cases the affected child seems to be the only affected family
Diseases resulting from
mitochondrial deletions of large parts of the mitochondrial DNA
molecule are usually sporadic without other affected family members.
Genetic counselling is complex for mitochondrial diseases.
Pre-natal testing is only available
for a few disorders.
How are Mitochondrial Diseases diagnosed?
Because of the multiple organ
systems involved and the variation in the age of onset,
mitochondrial diseases may be difficult to recognize. Even within
the same family the same disease may affect individuals differently.
A severe childhood disease such as Leigh’s syndrome may occur in
the same family with later onset adult neurodegenerative disease. In
some families mitochondrial myopathy has found some members with
deafness and diabetes in others strokes along with a mixture of
other symptoms. As well as the history and physical examination,
blood and urine specialized tests together with brain CT or MRI
scanning and skin and muscle biopsy are often needed to make a
diagnosis. Patients should be referred as soon as possible to a
specialist centre with expertise in metabolic and mitochondrial
What Treatments are available?
In the New Millennium treatments
for mitochondrial diseases are not very effective. Some effects of
these diseases can be treated such as cardiac arrhythmia, seizure
disorders, renal bicarbonate loss and hypoglycaemia.
When lactic acid accumulation seems
to be a major problem an experimental drug Dichloroacete DCA, will
lower the lactic acid. Although conclusive evidence of efficacy is
not yet available, most doctors working with mitochondrial diseases
treat their patients with cofactors and vitamins, which are thought
to help impaired metabolic pathways. These treatments include
combinations of Coenzyme Q10, L-Carnitine, Niacin, Thiamine, Biotin
and Riboflavin. Special diets can be helpful.
Some patient’s benefit by high
fat diets with restriction of simple carbohydrates. Fructose
restriction may help.
Other patients need high
carbohydrate intake with particular supplementation of complex
carbohydrates such as uncooked cornstarch.
Only with a through medical
evaluation, best carried out in a centre specializing in metabolic
& mitochondrial diseases, can the optimal treatment regime for
each patient be chosen.
What does the future hold? (1a)
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 mitochondrial dysfunction, and therefore 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 now being investigated. Whereas nuclear manipulation
would necessitate treatment for life, manipulation of the
mitochondrial genome would result in a one-off treatment thus
providing a “CURE” for Mitochondrial Disorders.