Complex I 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 pieces of the respiratory chain doesn’t work as well as it should. Complex I deficiency deficiency is related to the first step in the ETC. To learn more about the respiratory chain, please click here.

• Complex 1 deficiency
• NADH oxidoreductase deficiency
• NADH:Q(1) oxidoreductase deficiency
• NADH-coenzyme Q reductase deficiency

Complex I is the largest piece of the ETC, made up of many subunits. These subunits are coded in both mitochondrial genes (mtDNA), and nuclear genes (nDNA). Most of the time, complex I deficiency is inherited in an autosomal recessive pattern, but it can also be X-linked, mitochondrially inherited, or sporadic. People with the same genetic cause for complex I deficiency can also have different symptoms or be more severely affected than others, even in the same family.

Complex I deficiency is the most common mitochondrial disease in children (about 30% of cases). Overall complex I deficiency is found in around 1 in 8,500 people. There may be more people we don’t know about with complex I deficiency since many people with mitochondrial conditions are not diagnosed or are misdiagnosed, and complex I can cause many different symptoms that affect people differently.

Complex I deficiency causes a range of signs and symptoms. 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:

• Differences in brain function (encephalopathy)
• Seizures (epilepsy)
• Intellectual disability
• Trouble coordinating movement (ataxia)
• Involuntary movement (dystonia)
• Low muscle tone (hypotonia)
• Muscle pain (myalgia)
• Extreme fatigue or tiredness after activity (exercise intolerance)
• Lactic acidosis, which can cause nausea, vomiting, weakness and fast breathing
• Heart conditions
• Liver conditions
• Kidney conditions
• Vision problems like abnormal eye movement or breakdown of the optic nerve

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

Complex I deficiency can be diagnosed by:

• Blood tests for lactate levels 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 I deficiency
• A detailed physical exam and medical history
• Imaging tests like MRIs to look for changes in the brain

Complex I 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 I deficiency. Treatment and management of complex I deficiency is symptomatic and supportive. This may include:

• Physical therapy
• Nutritional support
• Medications based on symptoms like seizures or muscle spasms
• Avoidance of mitochondrial toxins like certain drugs, tobacco and alcohol
• Mitochondrial supplements
• Special schooling arrangements

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

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

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

• Mitochondrial complex I deficiency: MedlinePlus Genetics
• Mitochondrial complex I deficiency | About the Disease | GARD

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