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Disease Profile

Mitochondrial complex II 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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

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 2 mitochondrial respiratory chain deficiency; Succinate CoQ reductase deficiency; Mitochondrial respiratory chain complex II deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

Complex II deficiency is a 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. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood.[1] Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes.[1][2][3] In many cases the underlying gene mutations cannot be identified.[2] Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.[1]

Symptoms

The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood.[1] Many factors affect symptom and symptom severity, including what gene mutation is involved. Many genes must work together to ensure that the enzyme, complex II (succinate dehydrogenase), can perform its job normally in the body. Changes in the SDHA, SDHB, SDHC, SDHD, SDHAF1, or SDHAF2 genes can all potentially cause complex II deficiency.

Much of what we know today about the signs and symptoms of complex II deficiency are based on articles which describe individual patients. Due to the rarity of this condition and the complexity of its cause, it is very difficult to predict how a person will be affected. We strongly recommend that you work with your or your child’s healthcare provider to learn more about how the deficiency is affecting your or your child’s health. In the meantime, we have summarized symptoms of complex II deficiency which have been described in case reports:

Inheriting two SDHA gene mutations has caused myoclonic seizures and Leigh’s syndrome.[1][2] Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of people develop symptoms in adulthood or have symptoms that worsen more slowly. The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia) that leads to eating problems. Click here to visit Genetics Home Reference and learn more about Leigh syndrome.

Inheriting two SDHB gene mutations can cause leukodystrophy.[2] Leukodystrophies affect the myelin sheath, the material that surrounds and protects nerve cells. Damage to this sheath slows down or blocks messages between the brain and the rest of the body. This leads to problems with movement, speaking, vision, hearing, and mental and physical development. Most of the leukodystrophies appear during infancy or childhood. They can be hard to detect early because children seem healthy at first. However, symptoms gradually get worse over time. Click here to visit MedlinePlus.gov and learn more about leukodystprohy.

Inheriting two SDHAF1 gene mutations can cause severe progressive leukoencephalopathy beginning in infancy. Leukoencephalopathy refers to the degeneration of the white matter of the brain.  It is usually diagnosed by MRI. It causes cognitive impairment, increased muscle tone, and hyperactive reflexes.[1]

Inheriting two SDHD gene mutations can cause progressive loss of mental and movement abilities (psychomotor retardation), and seizures. Signs and symptoms may begin in infancy and progress through childhood.[1][2]

Complex II deficiency has also been described in association with dilated cardiomyopathy (and heart failure in childhood),[4] hemolytic uremic syndrome and rhabdomyolysis, congenital dislocation of the hip joint, progressive encephalomyopathy (a disorder affecting the brain and skeletal muscle, usually causing weakness) with dementia, and Kearns–Sayre syndrome.[2]

Case reports have also demonstrated that people who have only a single mutation in one of these genes may also be at risk for health problems:

Having one SDHA gene mutation caused optic atrophy, ataxia, proximal myopathy in adulthood.[5]

Having one mutation in the SDHA, SDHB, SDHC, SDHAF2, or SDHD gene can cause an increased risk for paragangliomas and/or pheochromocytomas.[1]

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
30%-79% of people have these symptoms
Abnormal left ventricular function
0005162
Babinski sign
0003487
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Distal amyotrophy
Distal muscle wasting
0003693
Easy fatigability
0003388
Generalized muscle weakness
0003324
Generalized myoclonic seizure
0002123
Hyperactive deep tendon reflexes
0006801
Hyperactive patellar reflex
Overactive knee reflex
0007083
Hyperreflexia in upper limbs
0007350
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Left ventricular hypertrophy
0001712
Motor delay
0001270
Motor deterioration
Progressive degeneration of movement
0002333
Progressive psychomotor deterioration
0007272
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Skeletal myopathy
0003756
Weight loss
0001824
5%-29% of people have these symptoms
Abnormal atrioventricular conduction
0005150
Ataxia
0001251
Expressive language delay
0002474
Feeding difficulties in infancy
0008872
Focal myoclonic seizure
0011166
Frequent falls
0002359
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Irritability
Irritable
0000737
Knee flexion contracture
0006380
Lower limb hypertonia
0006895
Mild microcephaly
0040196
Moderate global developmental delay
0011343
Noncompaction cardiomyopathy
0012817
Spastic paraparesis
0002313
Spastic tetraparesis
0001285
1%-4% of people have these symptoms
Blindness
0000618
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
External ophthalmoplegia
Paralysis or weakness of muscles within or surrounding outer part of eye
0000544
Loss of ability to walk
0006957
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pigmentary retinopathy
0000580
Poor head control
0002421
Vesicoureteral reflux
0000076
Percent of people who have these symptoms is not available through HPO
Abnormal mitochondria in muscle tissue
0008316
Autosomal recessive inheritance
0000007
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Decreased activity of mitochondrial complex II
0008314
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Dystonia
0001332
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

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.
  • The United Mitochondrial Disease Foundation (UMDF) has information on Getting a Diagnosis. Click on the UMDF hyperlink above to view the article.

    Treatment

    Treatment options for complex II deficiency may be similar to those for other mitochondrial disorders in general.[2] The United Mitochondrial Disease Foundation (UMDF) provides detailed information on treatment through their Web site at: https://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934635 We strongly recommend that you discuss this information with a healthcare provider.

    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.

        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 II deficiency. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Jackson CB et al.,. Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency. J Med Genet. 2014 Mar; 51(3):170-5. https://www.ncbi.nlm.nih.gov/pubmed/ 24367056. Accessed 4/16/2015.
            2. Ma YY et al.,. Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy. Brain Dev. 2014 May; 36(5):394-8. https://www.ncbi.nlm.nih.gov/pubmed/ 23849264. Accessed 4/16/2015.
            3. Alston CL et al.,. Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. J Med Genet. 2012 Sep; 49(9):569-77. https://www.ncbi.nlm.nih.gov/pubmed/ 22972948. Accessed 4/16/2015.
            4. Davili Z, Johar S, Hughes C, Kveselis D, Hoo J. Succinate dehydrogenase deficiency associated with dilated cardiomyopathy and ventricular noncompaction. Eur J Pediatr. 2007 Aug; 166(8):867-70. Accessed 4/21/2015.
            5. Birch-Machin MA et al.,. Late-onset optic atrophy, ataxia, and myopathy associated with a mutation of a complex II gene. Ann Neurol. 2000 Sep; 48(3):330-5. Accessed 4/16/2015.

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