Complex V 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 major complexes, or pieces, of the respiratory chain doesn’t work as well as it should. Complex V deficiency is related to the fifth and final step in the ETC. To learn more about the respiratory chain, please see click here.

• Complex 5 deficiency
• Mitochondrial complex V deficiency
• Mitochondrial complex 5 deficiency
• ATP synthase deficiency
• Isolated mitochondrial respiratory chain complex V deficiency
• ATPAF2 deficiency
• ATPase deficiency

MT-ATP6

The most common cause of complex V deficiency is changes in the mitochondrial gene MT-ATP6. 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 multiple nuclear genes have also been associated with complex V deficiency. When inherited from nuclear DNA, Complex V 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. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have complex V deficiency.

Both males and females can have complex V deficiency.

The prevalence of complex V deficiency is unknown. The condition may be underdiagnosed since it causes many different symptoms that affect people differently.

Both Male and Female

Complex V 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 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:

• Feeding problems
• Low muscle tone (hypotonia)
• Extreme fatigue (lethargy)
• Developmental delay
• Lactic acidosis, which can cause nausea, vomiting, weakness and fast breathing
• High levels of ammonia (hyperammonemia)
• Abnormal brain function (encephalopathy)
• Heart conditions (especially enlargement of part of the heart called cardiomyopathy)
• A pattern of facial features including a high forehead, curved eyebrows, downward pointed eyes, a large nose bridge, low-set ears, thin lips, and a small chin (micrognathia)

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

Complex V deficiency can be diagnosed by:

• Blood tests looking at the activity of complex V, levels of lactate, overall metabolic function and others
• Taking a small piece of muscle to look for changes in the mitochondria (muscle biopsy)
• Genetic testing for genes known to cause complex V 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 V 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 V deficiency. Treatment and management of complex V deficiency is typically symptomatic and supportive. This may include:

• Physical therapy
• Medications and/or surgeries based on symptoms
• Avoidance of mitochondrial toxins like certain drugs, tobacco and alcohol
• Mitochondrial supplements
• Special schooling arrangements

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

• Metabolic specialist or geneticist
• Dietitians (diet and nutrition)
• Physical, speech, and occupational therapists
• Neurologists (muscles and brain)
• Cardiologists (heart)

It is important that all those living with or caring for someone with complex V 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
• Neurology
• Nutritionist
• Physical and occupational therapy
• Registered dietitian

• Mitochondrial complex V deficiency: MedlinePlus Genetics
• https://rarediseases.info.nih.gov/diseases/18649/isolated-atp-synthase-deficiency
• From the Structural and (Dys)Function of ATP Synthase to Deficiency in Age-Related Diseases

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