Complex III Deficiency

Mitochondria are parts of a cell that help turn the energy we get from food into energy that the body can use. They are also important in the communication between body parts and creating other materials the body needs. Mitochondrial conditions can cause a variety of signs and symptoms in many parts of the body, particularly those that use a lot of energy like muscles and the brain.

The respiratory chain, also called the electron transport chain (ETC), helps a cell create energy (in the form of ATP) using oxygen. Mitochondrial respiratory chain disorders (MRCDs) are a group of conditions that happen when one of the five complexes, or pieces, of the respiratory chain doesn’t work as well as it should. Complex III deficiency is related to the third step in the ETC. To learn more about the respiratory chain, please click here.

• Complex 3 deficiency
• Isolated CoQ-cytochrome c reductase deficiency
• Ubiquinone-cytochrome c oxidoreductase deficiency
• Mitochondrial complex III deficiency
• Mitochondrial complex 3 deficiency

BCS1L, MT-CYB, UQCRFS1, CYC1, UQCRB, UQCRQ, UQCC2, TTC19, LYRM7, CYTB, UQCC3, and UQCRC2

The most common causes of complex III deficiency are changes in the genes BCS1L or MT-CYB. Complex III deficiency related to the gene BCS1L occurs when there are changes in both copies of the gene (autosomal recessive inheritance). Someone who has a change in only one copy of the gene is called a carrier, and they usually do not have any medical symptoms. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have complex III deficiency.

Complex III deficiency caused by changes in MT-CYB are mitochondrially inherited. Mitochondria are inherited from the mother through her eggs. People typically do not inherit any mitochondria from sperm, making it very unlikely for mitochondrial conditions to be passed down from a father.

Changes in other genes, UQCRFS1, CYC1, UQCRB, UQCRQ, UQCC2, TTC19, LYRM7, CYTB, UQCC3, and UQCRC2, have also been associated with complex III deficiency.

Both males and females can have complex III deficiency.

Complex III deficiency is thought to be very rare, and the exact number of people with the condition is unknown.

Complex III deficiency causes a range of signs and symptoms. Some people start showing life-threatening symptoms as a baby and die very early, where others may start showing muscle symptoms as an adult. Even people in the same family can have different symptoms or be more severely affected than others. Always check with your provider if new symptoms appear or you are concerned. Signs and symptoms may include:

• Low muscle tone (hypotonia)
• Low blood sugar (hypoglycemia) or episodes of extremely high blood sugar (hyperglycemia)
• Failure to thrive
• Changes in the brain (encephalopathy)
• Delayed development
• Lactic acidosis, which can cause nausea, vomiting, weakness and fast breathing
• Muscle weakness (myopathy)
• Difficulty communicating
• Extreme tiredness (fatigue) especially after activity (exercise intolerance)
• Liver conditions or liver failure
• Kidney conditions (especially tubulopathy)
• Heart conditions (especially cardiomyopathy) or heart failure

Some people with complex III deficiency have signs and symptoms that are diagnosed as a specific syndrome, like Leigh syndrome or spinocerebellar ataxia. Not everyone who has one of these conditions has complex III deficiency, since there are other causes for these syndromes.

Complex III deficiency can be diagnosed by:

• Blood tests for lactate and other levels, the activity of complex III, and overall metabolic function
• Taking a small piece of muscle to look for changes in the mitochondria (muscle biopsy)
• Genetic testing for genes known to cause complex III deficiency
• A detailed physical exam and medical history
• Imaging tests like MRIs or CTs to look for changes in the brain and other parts of the body

Complex III deficiency is not included on newborn screening panels.

No

Before beginning any treatment or therapy, please consult with your physician.

There is currently no FDA-approved therapy for complex III deficiency. Treatment and management of complex III deficiency is symptomatic and supportive. This may include:

• Physical therapy
• Medications based on symptoms
• Surgery based on symptoms such as eye procedures
• Avoidance of mitochondrial toxins like certain drugs, tobacco and alcohol
• Mitochondrial supplements
• Special schooling arrangements

Individuals living with complex III deficiency typically work with several healthcare providers regularly based on their symptoms, which may include:

• Metabolic specialist or geneticist
• Dieticians
• Physical, speech, and occupational therapists
• Neurologists
• Cardiologists
• Gastroenterologists
• Endocrinologists

It is important that all those living with or caring for someone with complex III deficiency have an emergency protocol letter. These letters, which are written and signed by a doctor, share details about prescribed treatment during a crisis and in emergency room settings.

• Cardiology
• Endocrinology
• Gastroenterology
• Neurology
• Nutritionist
• Physical and occupational therapy
• Registered dietitian

• Mitochondrial complex III deficiency: MedlinePlus Genetics
• https://rarediseases.info.nih.gov/diseases/8295/mitochondrial-complex-iii-deficiency

Connecting with others impacted by a rare disease allows for vital information to be shared about day-to-day life, prevents isolation, and gives hope. Please contact MitoAction for peer support opportunities at 888-MITO-411 or email mito411@mitoaction.org.

Other resources we recommend are:

• New Patient Kit for Mitochondrial Conditions
• Planning and Preparation
• Monthly Expert Series
• Energy in Action Podcast