Complex II 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 II deficiency is related to the second step in the ETC. To learn more about the respiratory chain, please click here.

• Complex 2 deficiency
• Succinate-CoQ reductase deficiency
• Mitochondrial respiratory chain complex II deficiency
• Succinate dehydrogenase deficiency
• Succinate-coenzyme Q reductase deficiency
• Succinate-ubiquinone reductase deficiency

Complex II is made up of 4 protein subunits called SDHA, SDHB, SDHC, and SDHD. Changes in genes that code for these subunits (SDHA, SDHB, and SDHD) can cause them not to work as well as they should. Changes in another gene, SDHAF1, can also impact complex II activity.

Complex II deficiency usually happens when there are changes in both copies of a related gene (autosomal recessive inheritance). Someone who has a change in only one copy of a related gene is called a carrier. Carriers for some genes related to complex II deficiency can be at an increased risk for certain types of cancer. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have complex II deficiency. Both males and females can have complex II deficiency.

People with the same genetic cause for complex II deficiency can also have different symptoms or be more severely affected than others, even in the same family.

Complex II deficiency is thought to be very rare, with fewer than 100 cases reported in the literature. An estimated II-4% of people with a known mitochondrial respiratory chain disorder (MRCD) have complex II deficiency.

Complex II deficiency causes a range of signs and symptoms. Some people start showing life-threatening symptoms as a baby, 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:

• Muscle weakness
• Extreme fatigue or tiredness after activity (exercise intolerance)
• Trouble coordinating movement (ataxia)
• Low muscle tone (hypotonia)
• Muscle pain (myalgia)
• Developmental delay
• Failure to thrive
• Intellectual disability
• Changes in the brain (leukoencephalopathy)
• Seizures (epilepsy)
• Lactic acidosis, which can cause nausea, vomiting, weakness and fast breathing
• Heart conditions
• Eye conditions
• Multiorgan failure
• Short stature

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

Complex II deficiency can be diagnosed by:

• Blood tests for lactate and pyruvate levels, the activity of complex II, 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 II 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 II 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 II deficiency. Treatment and management of complex II deficiency is symptomatic and supportive. This may include:

• Physical therapy
• Nutritional support
• Medications based on symptoms like seizures, muscle spasms or heart conditions
• 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 II deficiency typically work with several healthcare providers regularly based on their symptoms, which may include:

• Metabolic specialist or geneticist
• Dieticians
• Physical therapist
• Neurologists
• Cardiologists
• Optometrists or Ophthalmologists
• Endocrinologists

It is important that all those living with or caring for someone with complex II 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.

• Mitochondrial complex II deficiency, nuclear type 1 – National Organization for Rare Disorders
• GARD Rare Disease Information – Mitochondrial complex II 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