What Are Mitochondrial Diseases?

Mitochondrial diseases are chronic (long-term) genetic disorders that are often inherited. Mitochondrial disease or disorder refers to a group of disorders that affect the mitochondria. Mitochondria are tiny compartments found in almost every cell in our body. They act as the cell’s energy factory or power plant.

Mitochondrial disease occurs when the number or function of mitochondria in the cell is disrupted or defective. This causes problems for high-energy demanding organs such as the heart, muscles, and brain. This is due to the mitochondria failing to produce the amount of energy required for these organs to function correctly. 

As a result, if you suffer from a mitochondrial disease, you may experience prominent muscular problems or mitochondrial myopathies (‘myo’ meaning muscle and ‘patho’ meaning disease) or mitochondrial encephalomyopathies (‘encephalo’ refers to the brain) which cause prominent neurological problems as well as muscular.

This article will provide an overview of mitochondrial diseases by discussing the causes, symptoms, management and treatment of the diseases. It will help answer your questions regarding the life-changing disorder. 

Overview

Mitochondrial disease refers to a condition where the mitochondria, tiny structures within our cells, do not produce enough energy, which is known as ATP (adenosine triphosphate). These tiny structures are present in almost all of the cells within the body. Mitochondria are responsible for producing 90% of the energy our body needs to function properly.¹  Consequently, when there is dysfunction in the mitochondria, the body is unable to supply the required energy to support the normal function of its organs.

Each individual is uniquely impacted by mitochondrial disease, as it involves a complex interplay of functioning and malfunctioning mitochondria within the cells. Therefore, there is a huge variety in the severity and symptoms of mitochondrial disease depending on how many cells are affected and their location in the body. 

There are times when particular body systems are affected in a recognisable pattern. These patterns are given a specific name, such as Alpers disease, Leigh syndrome, MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), or MERRF (myoclonus epilepsy with ragged-red fibres).²

Mitochondrial diseases are usually progressive and have the potential to affect various parts of the body, including the cells of the brain, nerves, heart, kidneys, muscles, liver, eyes, ears, and pancreas. 

Causes of mitochondrial diseases

Mitochondria are remarkable structures within our cells that possess their own DNA, known as mitochondrial DNA or mtDNA. Some mitochondrial disorders may be caused by mtDNA mutations or mutations in the mitochondrial genes present in the nuclear DNA found in the cell’s nucleus. These mutations can arise from various factors, including exposure to environmental toxins.³

Primary mitochondrial disease is a genetic disorder that is commonly inherited. This means that a parent with the disease can pass on the disorder to their child. There are several ways in which the disorder can be passed down through generations.

To gain a complete understanding of inheritance types, it is important to delve into the role of genes and DNA. Genes play a crucial role in determining our traits and characteristics such as our eye colour. These genes consist of DNA, which contains the unique codes that shape our individual makeup.¹

Typically, offspring inherit genes in pairs: one gene from the father and another from the mother. However, a child with mitochondrial disease does not receive a normal pair of genes from their parents. Instead, one or both of the genes undergo a mutation. When a gene mutates, it becomes defective and changes. 

Understanding how mitochondrial disorders pass on from parent to child. will ultimately allow individuals to have a better chance at preventing the disorder from passing on.¹

Inheritance types in genetic conditions are as follows:

• Autosomal recessive inheritance: When a child receives one mutated copy of a gene from both parents. Both parents carry a mutated gene although they do not show symptoms of the condition. The likelihood that each child in the family will inherit a mitochondrial disease is 25%
• Autosomal dominant inheritance: A child receives one mutated copy of a gene from either of the parents. In this mode of inheritance, the parent carrying the mutant gene may exhibit symptoms or have the condition themselves. The likelihood that each child in the family will inherit a mitochondrial disease is 50%
• Mitochondrial inheritance: This unique type of inheritance involves the passing down of mitochondrial DNA to offspring. During sexual reproduction, the egg provides the mitochondria whereas the sperm only offers its DNA. Therefore, mothers with a mutation in their mitochondrial gene will pass on this defect to 100% of their offspring
• Random mutations: Occasionally, genes can develop mutations that are not inherited from a parent. These spontaneous mutations can occur during a person’s lifetime and are not related to the genetic material inherited from their parents¹

Signs and symptoms of mitochondrial diseases

Symptoms of mitochondrial disease depend on the number and location of mutated mitochondria present in the body. Symptoms of mitochondrial disease can vary in both severity and age of onset, even among individuals within the same family who share the condition.

Mitochondrial disorder symptoms include:

• Poor growth
• Muscle weakness and/or loss of muscle coordination 
• Neurological problems such as seizures
• Autism spectrum disorder
• Visual and/or hearing loss or problems
• Developmental delays or learning disabilities
• Heart, kidney or liver disease
• Gastrointestinal disorders such as severe constipation, diarrhoea or unexplained vomiting
• Diabetes mellitus
• Respiratory (breathing) disorders
• Increased risk of infection
• Thyroid and/or adrenal dysfunction
• Dysfunction of the autonomic nervous system
• Neuropsychological changes or dementia characterised by confusion, disorientation and memory loss^1,3

Management and treatment for mitochondrial diseases

At present, there is no cure or highly effective treatment for mitochondrial diseases. However, there are ways to help manage the disorder that can help reduce symptoms and slow the decline in health. Do note that there are new (novel) ways, such as mitochondrial donation, to prevent the disorder from being passed on to offspring via assisted reproductive treatments. We will be looking further into preventative measures later on.

The choice of treatment and management will vary from patient to patient and depends on the severity of the specific mitochondrial disease diagnosed. A patient’s response to any kind of treatment is unpredictable and, in the long run, it is difficult to predict the effect of the disease on the patient.

Treatments to help manage mitochondrial disease may include:

• Vitamins and supplements - inclusive of; coenzyme Q10, B complex vitamins like thiamine (B1) and riboflavin (B2), alpha-lipoic acid, L-carnitine (carnitor), creatine, and L-arginine
• Exercise - this includes both resistance/strength training and endurance exercises. These will help to increase muscle strength and size. Endurance exercises can include, but are not limited to, walking, swimming, running, dancing and cycling. Resistance/strength training includes exercises such as weight lifting, sit-ups, bicep curls, leg extensions, and others
• Conserving energy - it is crucial to not overexert yourself within a limited timeframe. Learn to pace yourself
• Other treatments - these may include physical therapy, speech therapy, respiratory therapy, and occupational therapy¹

Avoiding situations such as exposure to cold, heat, sleep deprivation, starvation, stressful situations, alcohol use, cigarettes, and monosodium glutamate (MSG, a flavour enhancer commonly used in processed foods) will help prevent your medical condition from worsening. 

FAQs

How are mitochondrial diseases diagnosed?

There is no single diagnostic test that can diagnose mitochondrial disease due to the vast number of organs and tissues the disease can affect. Referral to a medical facility with a physician who specialises in mitochondrial diseases is critical when getting a diagnosis.

Diagnosis starts with a series of tests and examinations that may include:

• A review of family history
• A full physical examination
• A neurological examination
• A metabolic examination that includes urine and blood tests and a spinal tap (cerebral spinal fluid test) if necessary

Depending on the patient’s symptoms and the areas of the body that are affected, other tests may include:

• For vision symptoms - a retinal exam or electroretinogram (ERG)
• For heart disease symptoms - an electrocardiogram (ECG) or echocardiogram
• For neurological symptoms - magnetic resonance imagining (MRI) or spectroscopy (MRS)
• For hearing symptoms - audiogram or auditory-brainstem evoked responses (ABER)
• Blood test - to detect thyroid dysfunction and perform genetic DNA testing¹

How can I prevent mitochondrial diseases?

New treatments are being investigated to assist mothers with mitochondrial disease to give birth to healthy children. These treatments involve altering the embryo’s complement of DNA by replacing the mother’s mitochondria with those from an egg donor. 

However, these types of treatments raise ethical, societal and safety issues alongside the fact that the changes made will be passed on to successive generations. Therefore, further research is underway to assess the safety and efficiency of such treatments. 

Who is at risk of mitochondrial diseases?

Individuals with mtDNA mutations face the risk of developing mitochondrial diseases. If a family member carries these mutations, there is a higher chance of inheriting the disease, as it is an inherited genetic disorder.

How common are mitochondrial diseases?

Mitochondrial myopathies (disorders that affect the muscles and are caused by mitochondrial defects) are somewhat common. Primary mitochondrial disorders are the most common inherited errors of metabolism. 

The prevalence of mitochondrial encephalomyopathies for preschool-aged children is 1 in 11,000. Mitochondrial disease caused by mutations in mitochondrial DNA has an estimated prevalence of 1 in 5,000, and 1 in 35,000 suffer a mitochondrial disease caused by mutations in the nuclear DNA.⁴

When should I see a doctor?

If a child presents with non-specific symptoms such as mental retardation, learning disorders, epilepsy or multisystem failure, they must be seen by a specialist health professional, as the possibility of a mitochondrial disease should be considered with the presentation of these symptoms. 

Summary

Mitochondrial diseases are incurable genetic disorders that occur when mutations take place in the mitochondrial DNA or mitochondrial genes within the nuclear DNA. They are often inherited, meaning those who have parents with a mitochondrial disease will have an increased chance of inheriting it themselves. There are also other triggers such as environmental toxins. 

Research into treatment for mitochondrial diseases is ongoing; there are associated ethical, societal and safety concerns with treatment plans that have been developed thus far for mitochondrial disorders. Rapid technological and medical advancement in the field of metabolic disorders will soon allow for a greater pool of preventative and treatment options for individuals affected by mitochondrial diseases.