Rare Nephrology News

Disease Profile

Mitochondrial complex III deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

G71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Complex 3 mitochondrial respiratory chain deficiency

Categories

Congenital and Genetic Diseases; Metabolic disorders

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]

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]

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.

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
Seizure
0001250
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Tubulointerstitial nephritis
0001970

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.

    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

      Organizations Providing General Support

        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 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.

            References

            1. Overview of Mitochondrial Diseases. NAMDC. https://rarediseasesnetwork.epi.usf.edu/NAMDC/learnmore/index.htm. Accessed 4/3/2011.
            2. Cassandra L. Kniffin. MITOCHONDRIAL COMPLEX III DEFICIENCY. OMIM. November 29, 2010; https://www.ncbi.nlm.nih.gov/omim/124000. Accessed 4/3/2011.
            3. Treatments & Therapies. United Mitochondrial Disease Foundation. https://www.umdf.org/site/c.otJVJ7MMIqE/b.5692887/k.6686/Treatments__Therapies.htm. Accessed 4/3/2011.
            4. Facts About Mitochondrial Myopathies. Muscular Dystrophy Association. April 2010; https://www.mdausa.org/publications/mitochondrial_myopathies.html#whatare. Accessed 4/4/2011.
            5. Types of Mitochondrial Disease. United Mitochondrial Disease Foundation. https://www.umdf.org/site/c.otJVJ7MMIqE/b.5692881/k.4B7B/Types_of_Mitochondrial_Disease.htm#Complex3. Accessed 4/4/2011.
            6. Histiocytoid cardiomyopathy. Orphanet. May 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137675. Accessed 8/29/2011.

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