Mitochondrial Genetic Disorders: What You Need to Know

An estimated 1,000 to 4,000 infants are born with a mitochondrial genetic disorder in the United States every year. Many of these disorders are quite serious.

In this article we look more closely at what mitochondria are and the functions they serve in the human body. We will also examine some of the more common mitochondrial genetic diseases and the potential of gene therapy in developing a cure.

What are mitochondria?

Every living organism is comprised of cells: tiny components contained in a membrane. Cells are the building blocks of life. They are the smallest organic unit that can engage in reproduction.

Cells are made up of organelles. Organelles perform a variety of functions. Mitochondria generate energy. Without them, the cell, and ultimately the organism, cannot survive.

Mitochondria are present in virtually every cell in the human body with the exception of red blood cells. Known as cell “powerhouses,” mitochondria absorb proteins, fats and sugars from our diet, refining them in a complicated chemical process in order to generate energy.

What functions do mitochondria serve?

Mitochondria are shaped to maximize productivity. They have an outer membrane and an inner membrane. The inner membrane consists of many layers to protect the mitochondria’s core, known as the “matrix.” The matrix contains fluid, ribosomes, and DNA as well structures known as “granules.”

In addition to generating energy, mitochondria also synthesize chemicals necessary for other processes within the human body. These include chemicals that break down waste products to render them less harmful and those that recycle waste products in order to conserve energy.

Mitochondria also tell cells when to die. This may sound counterintuitive, but the ability for cells to die off is intrinsic to healthy growth and development. If cells grow unchecked and do not die off as they should, this can result in a tumor.

What happens when mitochondria don’t work properly?

In order to produce energy, mitochondria need oxygen. They process amino acids in a carefully controlled way, producing chemical energy in a process known as “oxidative phosphorylation.” Just as oxygen is necessary for fire, it is also vital to this chemical process. Without oxygen, mitochondria simply cannot function, and the cell begins to die.

Mitochondria are integral to many essential processes within our cells. As a result, if mitochondria feature a genetic defect, this can have a severe impact upon human health.

What are the most common mitochondrial diseases?

The term “mitochondrial disease” encompasses a broad range of illnesses. Each involve a greater or lesser degree of mitochondrial disfunction.

Because mitochondria perform site-specific cellular functions, mitochondrial diseases come in hundreds of different forms. The following are some of the most common:

Alpers disease

This progressive neurodevelopmental disorder usually manifests in early childhood. The main symptoms are: psychomotor regression, liver disease, and seizures.

Infants born with Alpers disease may develop normally for weeks, and sometimes years, before the onset of symptoms. Typical symptoms include exaggerated reflexes with increased muscle tone, seizures, and a decline in cognitive ability.

Approximately 80 percent of infants with the condition develop symptoms by the age of 2. There is no known cure for Alpers disease, though clinicians can use anticonvulsants to treat seizures.

Leighs disease

This severe neurological disorder usually causes symptoms in the first year of life. It leads to a progressive decline in cognitive and movement abilities and can cause death by respiratory failure.

Initial symptoms of Leighs disease include diarrhea, vomiting, and difficulty swallowing and eating. A small number of people with this genetic disorder do not develop symptoms until adulthood. As the disease progresses, it can cause rapid involuntary eye movements; degeneration of optic nerves; and severe respiratory impairment.

There is currently no known cure for the disorder. Specialists may use targeted treatments to relieve individual symptom, such as the administration of thiamine.

Mitochondrial myopathy

This type of mitochondrial disease causes symptoms such as: muscle weakness; fatigue; limited eye muscle movement and paralysis; blindness; cardiomyopathy; fatty liver; liver failure; difficulty swallowing; vomiting; chronic diarrhea; diabetes; symptoms of intestinal obstruction; Fanconi’s syndrome; seizures; spasms; developmental delay; deafness; dementia; and stroke.

Once incurred, any damage caused by mitochondrial myopathy is irreversible. However, movement, strength, function, and general health can be drastically improved through targeted therapies and dietary supplements.

What is the potential for gene therapy in treating mitochondrial diseases?

Researchers are increasingly turning to gene therapy as a potential cure for mitochondrial disease. Scientists have developed a genome-editing tool that could one day prove pivotal in the treatment of a range of mitochondrial disorders.

A UK-led study at the University of Cambridge targeted damaged DNA using an experimental gene therapy treatment. It allowed researchers to eliminate damaged mitochondria. Scientists hope this advancement could pave the way for tackling mitochondrial disorders on a cellular level by targeting the cause rather than merely treating the symptoms.

Researchers involved in the project hope to proceed to clinical trials in the near future. With an estimated 1 in 5,000 people affected with these serious and potentially fatal disorders, the ability to effectively erase mitochondrial mutations at a cellular level offers hope to many.