Mitochondrial complex III deficiency

Title

Other Names:

Complex 3 mitochondrial respiratory chain deficiency

Categories:

Congenital and Genetic Diseases; Metabolic disorders

Summary Summary

Mitochondrial complex III deficiency is one of several conditions caused by dysfunction of mitochondria, which are specialized compartments in cells that generate more than 90% of the energy required by the body.^[1] It is a severe, multisystem disorder that includes features such as lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Involvement of internal organs, including liver disease and renal tubulopathy, may also occur. Symptoms typically begin at birth. Many affected individuals die in early childhood, but some have survived longer. It is generally caused by mutations in nuclear DNA in the BCS1L, UQCRB and UQCRQ genes and inherited in an autosomal recessive manner. However, it may also be caused by mutations in mitochondrial DNA in the MTCYB gene, which is passed down maternally or occurs sporadically and may result in a milder form of the condition.^[2] Treatment generally focuses on alleviating symptoms and/or slowing down the progression of the disease, and effectiveness can vary among individuals.^[3]

Last updated: 4/4/2011

Symptoms Symptoms

The signs and symptoms of mitochondrial complex III deficiency are not the same for each affected individual, because a person with mitochondrial disease can have a unique mixture of healthy and defective mitochondria, with a unique distribution in the body.^[4] Several forms of mitochondrial complex III deficiency have been identified, and they are generally grouped based on the age of onset, nature and severity of symptoms.

The most severe form begins in infancy and causes life-threatening muscle and nervous system dysfunction (encephalomyopathy), lactic acidosis at birth, hypotonia (poor muscle tone), dystrophic posturing, seizures, and coma. Ragged-red fibers, a characteristic microscopic abnormality observed in muscle biopsy, are commonly present with this form.^[5]

In some individuals, encephalomyopathy does not begin until childhood or adulthood. For these individuals, symptoms may include various combinations of weakness, short stature, ataxia (inability to coordinate muscle movements), dementia, hearing loss, sensory neuropathy, pigmentary retinopathy (a disorder of the retina characterized by deposits of pigment and vision loss), and possible lactic acidosis or other features. Ragged-red fibers are common in these individuals as well.^[5]

Individuals with a less severe type may have myopathy with exercise intolerance that progresses to general weakness. Ragged-red fibers and lactic acidosis may be present.^[5]

A fourth described form is characterized by infantile histiocytoid cardiomyopathy.^[5] This is a condition characterized by cardiomegaly (enlarged heart), severe cardiac arrhythmias or sudden death, and the presence of histiocyte-like cells within the heart muscle.^[6]

Last updated: 8/29/2011

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
5%-29% of people have these symptoms
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Percent of people who have these symptoms is not available through HPO
Abnormality of the abdominal wall		0004298
Abnormality of the coagulation cascade		0003256
Aminoaciduria	High urine amino acid levels Increased levels of animo acids in urine [ more ]	0003355
Ataxia		0001251
Autosomal recessive inheritance		0000007
Brittle hair		0002299
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Cerebellar atrophy	Degeneration of cerebellum	0001272
Cerebral atrophy	Degeneration of cerebrum	0002059
Cholangitis	Bile duct inflammation	0030151
Cholestasis	Slowed or blocked flow of bile from liver	0001396
Decreased liver function	Liver dysfunction	0001410
Decreased mitochondrial complex III activity in liver tissue		0006558
Depressivity	Depression	0000716
EEG abnormality		0002353
Elevated hepatic transaminase	High liver enzymes	0002910
Emotional lability	Emotional instability	0000712
Exercise intolerance	Decreased ability to exercise Inability to exercise [ more ]	0003546
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Feeding difficulties in infancy		0008872
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
Hallucinations	Hallucination Sensory hallucination [ more ]	0000738
Hyperreflexia	Increased reflexes	0001347
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Hypoglycemia	Low blood sugar	0001943
Increased serum lactate		0002151
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Lactic acidosis	Increased lactate in body	0003128
Metabolic acidosis		0001942
Microvesicular hepatic steatosis		0001414
Mitochondrial encephalopathy		0006789
Mitochondrial inheritance		0001427
Muscle weakness	Muscular weakness	0001324
Muscular hypotonia	Low or weak muscle tone	0001252
Ragged-red muscle fibers		0003200
Rhabdomyolysis	Breakdown of skeletal muscle	0003201
Rod-cone dystrophy		0000510
Seizures	Seizure	0001250
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Tubulointerstitial nephritis		0001970

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
You can submit a question to Ask the Mito Doc, a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The North American Mitochondrial Disease Consortium (NAMDC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Mitochondrial complex III deficiency. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Mitochondrial complex III deficiency:
North American Mitochondrial Disease Consortium (NAMDC) Contact Registry
Mitochondrial Disease Community Registry

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 1-888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: https://www.mitoaction.org/
Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: resourcecenter@mdausa.org
Website: https://www.mda.org
The Mitochondria Research and Medicine Society
PO Box 55322
BLSC Building, Room # 3-316
Elm and Carlton Streets
Birmingham, AL
Telephone: 716-907-4349
Fax: 716-845-1047
E-mail: contact@mitoresearch.org
Website: http://www.mitoresearch.org
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Parent and Caregiver Resources

In this NCATS Video Profile, Stephanie Perron shares the story of her son’s life with a mitochondrial disease.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Mitochondrial complex III deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides a current, expert-authored, peer-reviewed, full-text article on mitochondrial disorders. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Mitochondrial complex III deficiency. Click on the link to view a sample search on this topic.

News & Events News & Events

NCATS Co-Sponsored Conferences

Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base Tuesday, December 2, 2014 - Wednesday, December 3, 2014
Location: NIH Campus, Bethesda, MD
Description: The goal of this meeting is to explore the use of nutritional interventions, including dietary supplements, in primary mitochondrial disorders (PMD); identify gaps in knowledge; develop a research agenda; and identify research opportunities to promote an evidence base for the use of nutritional interventions in primary mitochondrial disorders.

Contact: Kathryn Camp, MS, RD, CSP,(301) 435-3608, campkm@od.nih.gov

Co-funding Institute(s): Office of Dietary Supplements, Office of Rare Diseases Research

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Is complex III in the mitochondria itself or is it part of the body? I am confused about where exactly it is and what function it has. See answer
Are difficulty breathing and severe headaches symptoms of this condition? See answer

Have a question? Contact a GARD Information Specialist.