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; Isolated mitochondrial respiratory chain complex I deficiency; Isolated NADH-coenzyme Q reductase deficiency; Isolated NADH-CoQ reductase deficiency; Isolated NADH-ubiquinone reductase deficiency; Isolated complex I 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 helpful in some case but 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

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
100% of people have these symptoms
Decreased activity of mitochondrial complex I		0011923
80%-99% of people have these symptoms
Abnormal mitochondria in muscle tissue		0008316
Ataxia		0001251
Encephalopathy		0001298
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Focal T2 hyperintense brainstem lesion		0012748
Global developmental delay		0001263
Hepatomegaly	Enlarged liver	0002240
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Hypoglycemia	Low blood sugar	0001943
Increased CSF lactate		0002490
Increased serum pyruvate		0003542
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Lactic acidosis	Increased lactate in body	0003128
Lethargy		0001254
Leukodystrophy		0002415
Leukoencephalopathy		0002352
Mitochondrial myopathy		0003737
Muscular hypotonia	Low or weak muscle tone	0001252
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Optic disc pallor		0000543
Optic neuropathy	Damaged optic nerve	0001138
Paroxysmal involuntary eye movements		0007704
Poor eye contact		0000817
Poor head control		0002421
Proximal tubulopathy		0000114
Ptosis	Drooping upper eyelid	0000508
Respiratory insufficiency	Respiratory impairment	0002093
Sensorineural hearing impairment		0000407
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Vomiting	Throwing up	0002013
5%-29% of people have these symptoms
Blindness		0000618
Diabetes mellitus		0000819
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Fetal distress		0025116
Microcephaly	Abnormally small skull Small head circumference Reduced head circumference Decreased size of skull Decreased circumference of cranium [ more ]	0000252
Percent of people who have these symptoms is not available through HPO
Acute necrotizing encephalopathy		0006965
Autosomal recessive inheritance		0000007
Babinski sign		0003487
Cerebellar atrophy	Degeneration of cerebellum	0001272
Cerebral edema	Swelling of brain	0002181
Coma		0001259
Decreased activity of mitochondrial respiratory chain		0008972
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Dyskinesia	Disorder of involuntary muscle movements	0100660
Exercise intolerance	Decreased ability to exercise Inability to exercise [ more ]	0003546
Feeding difficulties in infancy		0008872
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Growth delay	Delayed growth Growth deficiency Growth failure Growth retardation Poor growth Retarded growth [ more ]	0001510
Hepatic failure	Liver failure	0001399
Hyperreflexia	Increased reflexes	0001347
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Mitochondrial inheritance		0001427
Progressive macrocephaly	Progressively abnormally enlarging cranium Progressively abnormally enlarging skull [ more ]	0004481
Respiratory failure		0002878
Seizure		0001250
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
X-linked dominant inheritance		0001423

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

Last updated: 2/1/2021

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.

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

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 MedlinePlus Genetics.

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 related to Mitochondrial complex I deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
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 I 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 I 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 Providing General Support

MitoAction
PO Box 310
Novi, MI 48376
Toll-free: 888-648-6228
E-mail: info@mitoaction.org
Website: https://www.mitoaction.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.

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

MedlinePlus Genetics contains information on Mitochondrial complex I 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 I deficiency. Click on the link to view a sample search on this topic.

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.

Have a question? Contact a GARD Information Specialist.

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.