Mitochondrial complex II deficiency

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]