Mitochondrial complex I deficiency

Title

Other Names:

Complex 1 mitochondrial respiratory chain deficiency; NADH coenzyme Q reductase deficiency; Mitochondrial NADH dehydrogenase component of complex I, deficiency of; Complex 1 mitochondrial respiratory chain deficiency; NADH coenzyme Q reductase deficiency; Mitochondrial NADH dehydrogenase component of complex I, deficiency of; NADH:Q(1) Oxidoreductase deficiency See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary Summary

Mitochondrial complex I deficiency is a type of mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. Complex I is the first step in a chain reaction in mitochondria leading to energy production. Signs and symptoms of complex I deficiency vary widely in nature and severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Features may include macrocephaly (large head) with progressive leukodystrophy, encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. The disease is caused by mutations in any of many genes and the inheritance pattern depends on the responsible gene. Treatment is only sometimes effective and may include metabolic therapies such as riboflavin, thiamine, biotin, co-enzyme Q10, carnitine, and a ketogenic diet (a special high-fat, low-carbohydrate diet).^[1]^[2]

Last updated: 4/18/2014

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormal mitochondria in muscle tissue	-
Acute necrotizing encephalopathy	-
Ataxia	-
Autosomal recessive inheritance	-
Babinski sign	-
Blindness	-
Cerebellar atrophy	-
Cerebral edema	-
Coma	-
Developmental regression	-
Exercise intolerance	-
Failure to thrive	-
Feeding difficulties in infancy	-
Growth delay	-
Hepatic failure	-
Hyperreflexia	-
Hypertrophic cardiomyopathy	-
Hypoglycemia	-
Hyporeflexia	-
Increased CSF lactate	-
Lactic acidosis	-
Lethargy	-
Leukodystrophy	-
Mitochondrial inheritance	-
Muscle weakness	-
Muscular hypotonia	-
Nystagmus	-
Optic disc pallor	-
Phenotypic variability	-
Progressive macrocephaly	-
Ptosis	-
Respiratory failure	-
Seizures	-
Sensorineural hearing impairment	-
Skeletal muscle atrophy	-
Spasticity	-
Strabismus	-
Vomiting	-
X-linked dominant inheritance	-

Last updated: 9/1/2016

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.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

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.

Prognosis Prognosis

There can be a lot of variability in the signs, symptoms and severity for people with mitochondrial complex I deficiency.^[3] Therefore, the long-term outlook (prognosis) varies among affected people.

In isolated complex I deficiency, the majority of affected people develop symptoms during the first year of life. Most people with this type have a rapidly progressive disease course and do not survive beyond childhood.

In other cases, signs and symptoms can range, causing an affected person to have any of the following:

fatal neonatal lactic acidosis - this is typically rapidly progressive, resulting in death in infancy
infantile-onset Leigh syndrome - affected children typically have normal early development but develop symptoms in late infancy or early childhood with progressive neurological abnormalities
childhood-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome - symptoms usually begin in childhood with seizures, migraines, vomiting, exercise intolerance, proximal limb weakness and short stature
adult-onset syndromes of encephalomyopathy (brain and muscle disease) with variable severity

There have also been some affected people who have had involvement of only one organ (for example, isolated hypertrophic cardiomyopathy (HCM) or Leber hereditary optic neuropathy).^[4]

Because not all people with this condition are affected the same way, the life expectancy may differ considerably.

Last updated: 4/22/2014

Do you have updated information on this condition? Let us know.

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

ClinicalTrials.gov lists trials that are studying or have studied Mitochondrial complex I deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Patient Registry

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. The North American Mitochondrial Disease Consortium (NAMDC) has a registry for patients who wish to be contacted about clinical research opportunities.

For more information on the registry see: http://rarediseasesnetwork.epi.usf.edu/registry/index.htm

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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: 888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: http://www.mitoaction.org
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 888-317-8633
Telephone: 412-793-8077
Fax: 412-793-6477
E-mail: info@umdf.org
Website: http://www.umdf.org

Do you know of an organization? Send us your suggestions.

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.

Genetics 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 GeneTests, 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.

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.

In-Depth Information

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 I 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
2013 Neurobiology of Disease in Children Symposium: Mitochondrial Disease Wednesday, October 30, 2013 - Wednesday, October 30, 2013
Location: Austin, TX
Description: The topic for the 2013 NDC Symposium is Mitochondrial Disease. The NDC Symposium is a forum for preeminent investigators assembled to discuss recent accomplishments and future directions with a large group of child neurologists, program officers from the National Institutes of Health, and members of dedicated foundations and associations.

Contact:

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 38KB)

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

What is the average life span of a person with this condition? See answer

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References References

Cassandra L. Kniffin. MITOCHONDRIAL COMPLEX I DEFICIENCY. OMIM. September 17, 2013; http://www.omim.org/entry/252010. Accessed 4/18/2014.
Types of Mitochondrial Disease. United Mitochondrial Disease Foundation. http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934629. Accessed 4/18/2014.
Patrick F Chinnery. Mitochondrial Disorders Overview. GeneReviews. September 16, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1224/. Accessed 4/22/2014.
Fassone E, Rahman S. Complex I deficiency: clinical features, biochemistry and molecular genetics. J Med Genet. September, 2012; 49(9):578-590. Accessed 4/22/2014.