Mitochondrial complex II deficiency, which is also known as CII deficiency, is a rare form of an inherited inborn error of metabolism (IEM). CII deficiency is an autosomal recessive disorder that arises from mutations in the succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC and SDHD). These genes code for the mitochondrial enzyme known as succinate dehydrogenase, a multicomponent, membrane-bound enzyme, which is also known as SDH, succinate-coenzyme Q reductase (SQR), or respiratory complex II. SDH is found in the inner mitochondrial membrane and catalyzes the oxidation of succinate to fumarate with the reduction of ubiquinone to ubiquinol. SDH or complex II is assembled via the action of two assembly factors (SDHAF1 and SDHAF2). Mutations in SDHA and SDHAF1 are most commonly found in patients with CII deficiency. Because complex II is found in the mitochondria, CII deficiency is technically considered a mitochondrial disease. CII deficiency accounts for between 2%-23% of all respiratory chain deficiency diagnoses. 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. The symptoms are very much dependent on the mutations to the SDH components. SDHA gene mutations cause myoclonic seizures and Leigh’s syndrome, a severe neurological disorder that is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within 1-2 years. SDHB gene mutations can cause leukodystrophy which affects the myelin sheath, the material surrounding and protecting nerve cells. Damage to the myelin sheath slows down or blocks messages between the brain and the rest of the body, which leads to problems with movement, speech, vision, hearing, and mental and physical development. SDHAF1 gene mutations can cause severe progressive leukoencephalopathy, which is characterized by the degeneration of the white matter of the brain. Interestingly, complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.

Mitochondrial Complex II Deficiency References

Citric Acid Cycle References