Mitochondrial disorders, also called mitochondrial cytopathies, are a
diverse group of diseases caused by damage to small structures found in
human cells that are essential in converting food to energy. The result is
decreased energy production and associated symptoms.
Cells are the building blocks of the human body, microscopic structures
that are bound by a membrane and contain numerous components called
organelles that are responsible for functions such as cell reproduction,
transportation of materials, and protein synthesis. Cellular respiration,
a process by which food molecules are converted into high-energy molecules
used as a source of energy, takes place in structures called mitochondria.
The energy produced by mitochondria is essential for cell functions.
Before the mid-twentieth century, little was known about mitochondrial
disorders. The first diagnosis of a mitochondrial disorder occurred in
1959, and the genetic material of microchondria, called mtDNA, was
discovered in 1963. In the 1970s and 1980s, as more was learned about the
mitochondria and more mitochondrial disorders were discovered, the term
"mitochondrial myopathies" (myopathy meaning a disease of
muscle tissue) was coined to describe the group of diseases. Further
research in the 1990s led to classification of mitochondrial disorders. As
it became evident that tissues other than muscle could be affected by
mitochondrial defects, the term "mitochondrial cytopathies"
(cytopathy meaning cell disorder) was adopted.
Disorders in which skeletal muscle is the primary target of the
mitochondrial dysfunction are called mitochondrial
. Mitochondrial encephalomyopathies are disorders in which muscle and
brain tissue is involved.
As of 2004 there were more than 40 distinct mitochondrial cytopathies.
Some of the more common disorders include:
Approximately 1,000 to 4,000 children are born with mitochondrial disease
in the United States each year. Typically, by the age of ten,
approximately one in 4,000 American children is diagnosed with
Causes and symptoms
Although mitochondrial disorders may be caused by distinctly different
damage to the mitochondrial genetic material, and thus affect any of the
hundreds of chemical reactions required to convert food and oxygen into
energy, they all share a common feature: the ability of mitochondria to
generate energy is damaged. Byproducts of the numerous reactions can begin
to accumulate in the cells and interfere with other chemical reactions and
over time damage the mitochondria further.
In many cases, a mitochondrial disorder is passed genetically from parent
to child (inheritance). It can often be helpful for the type of
inheritance to be determined, as parents can then make an educated
decision about the risks of passing the condition on to another child or
the risks of another
member developing the disease. Genetic defects may be passed through
nuclear DNA (nDNA), the genetic material found in each cell that
determines the majority of hereditary characteristics, or through mtDNA.
Some types of mitochondrial disorder inheritance include:
In some cases, no other family members are affected by the disease and
there appears to be no genetic link. These cases are called random or
sporadic occurrences and may be caused by a number of environmental
factors including certain drugs (e.g. medications used to treat human
virus [HIV] have been linked to mitochondrial damage),
(a disease characterized by self-starvation), exposure to certain toxins,
prolonged periods of insufficient oxygen, or older parental age (mtDNA
mutations may accumulate over time).
Because more than 90 percent of the energy needed by the human body to
function is generated by mitochondria, the effects of mitochondrial
disorders can be farreaching. Research has shown that cells of the brain,
nerves, skeletal muscles, liver, heart, kidneys, ears, eyes, and pancreas
seem to be particularly affected because of their high energy
requirements. Some of the more common symptoms of mitochondrial diseases
by organ system include the following:
Other symptoms include
failure to thrive
in infants, poor growth, short stature, fatigue, respiratory disorders,
swallowing difficulties, and increased risk of infection.
The array of symptoms that are displayed by children suffering from
mitochondrial disorders are common to many other diseases, and the age of
onset can range from early infancy to adulthood. Often, the hallmark sign
of a mitochondrial disorder that distinguishes it from other diseases with
similar symptoms is additional features (such as the above symptoms) that
do not normally appear with the non-mitochondrial disease. Parents should
notify their healthcare provider if their child develops symptoms atypical
for their previously diagnosed condition or if those symptoms get worse or
recur with infection.
Because of the complex nature of mitochondrial disorders, physicians take
a multi-faceted approach to diagnosing such diseases. The process usually
starts with a comprehensive physical exam and evaluation of the
patient's medical and family history. Often a neurological exam is
performed to determine if there are any brain abnormalities. To diagnose a
mitochondrial disorder and rule out other diseases, more extensive tests
may need to be performed. Some examples are as follows:
In some cases, a physician may not be able to diagnose the patient with a
specific mitochondrial disorder even after extensive evaluation. Parents
should, therefore, be advised that despite the complexity of testing for
mitochondrial disorders, diagnosis is not always possible.
As of 2004, there are no cures for mitochondrial disorders. Treatment
plans focus on delaying progression of the disease or reducing a
patient's symptoms. The method of treatment depends on many
factors, including the patient's disease, age, affected organs, and
health status. Not all patients benefit from treatment; those with less
severe disease generally respond better. Treatment may consist of
, supplements, physical or occupational therapy, or traditional
medications. Examples of these include:
For some patients, avoiding physiological stressors such as extreme cold,
extreme heat, poor
, fasting, and lack of
may improve their condition. Alcohol, cigarette smoke, and monosodium
glutamate (MSG, added to many Asian foods) may also exacerbate a
In some cases, a properly devised diet is necessary to avoid worsening
symptoms. Parents of a child affected with a mitochondrial disorder may be
referred to a dietician to help formulate a diet specific to his or her
disease. The plan is individualized to the child and may include
suggestions such as avoiding long periods of time without eating, eating
small but frequent meals, increasing or decreasing the amount of fat
consumed, and avoiding or supplementing with certain vitamins or
The prognosis of mitochondrial disease depends on many factors, including
the specific disorder, the mode of inheritance, the age of onset, and what
organs are affected. Two children suffering from the same mitochondrial
disorder may have two distinctly different courses. In some cases,
patients may be able to control their symptoms to a great degree with
various treatments, or progression of the disease is slow. In other cases,
the disease progresses rapidly and inevitably leads to death.
Prevention of inherited mitochondrial disorders is not possible unless
parents decide against having more children. In the case of mitochondrial
cytopathies that are caused by environmental factors such as certain drugs
or toxins, avoidance of these substances may minimize the risk of
developing mitochondrial disease.
Because of the potential of passing on inherited mitochondrial disorders
to other children, parents may be interested in genetic counseling.
Genetic counselors are health professionals who are trained to help
families determine the risk or probability of developing or passing on a
genetic disorder. Genetic testing, however, cannot determine with
certainty if or when a child will develop a mitochondrial disease or what
the severity will be.
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Adults: What We Know So Far."
Cleveland Clinic Journal of Medicine
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8085 Saltsburg Rd., Suite 201, Pittsburgh, PA 15239. Web site:
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Stephanie Dionne Sherk