Isolated succinate-CoQ reductase deficiency

Isolated succinate-CoQ reductase deficiency, also known as mitochondrial complex II deficiency, is a rare inherited disorder of the mitochondrial respiratory chain. It is caused by defects in succinate dehydrogenase (SDH), which functions as both complex II of the electron transport chain and as succinate dehydrogenase in the citric acid cycle. This enzyme complex is unique among the respiratory chain complexes because all four of its subunits (SDHA, SDHB, SDHC, SDHD) and its assembly factors (SDHAF1, SDHAF2) are encoded entirely by nuclear DNA rather than mitochondrial DNA. The disease primarily affects organs and tissues with high energy demands, including the brain, skeletal muscles, and heart. Clinical presentations are highly variable and can include Leigh syndrome (a progressive neurodegenerative disorder), leukoencephalopathy, hypertrophic or dilated cardiomyopathy, exercise intolerance, muscle weakness (myopathy), psychomotor regression, and failure to thrive. Some patients present in infancy or early childhood with severe encephalopathy, while others may have a later onset with milder symptoms such as isolated myopathy or optic atrophy. Lactic acidosis is a common biochemical finding. There is currently no cure for isolated succinate-CoQ reductase deficiency. Treatment is primarily supportive and symptomatic, and may include supplementation with riboflavin (vitamin B2) and coenzyme Q10, which have shown benefit in some patients. Management also involves nutritional support, physical therapy, and treatment of specific complications such as seizures or cardiac dysfunction. Prognosis varies widely depending on the severity and specific genetic cause, ranging from fatal infantile presentations to milder forms compatible with longer survival.

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