Complex 2 mitochondrial respiratory chain deficiency

Complex II Mitochondrial Respiratory Chain Deficiency

Complex II mitochondrial respiratory chain deficiency is a rare genetic disorder that affects the function of mitochondria, the energy-producing structures within cells. This condition is characterized by a deficiency in the activity of Complex II, also known as succinate dehydrogenase (SDH), which is a critical component of the mitochondrial respiratory chain.

Overview

Mitochondria are responsible for generating adenosine triphosphate (ATP), the primary energy currency of the cell, through a process known as oxidative phosphorylation. The mitochondrial respiratory chain consists of five complexes (I-V) that work together to transfer electrons and pump protons across the inner mitochondrial membrane, creating a proton gradient that drives ATP synthesis.

Complex II, or succinate dehydrogenase, is unique among the respiratory chain complexes because it is also part of the citric acid cycle (Krebs cycle). It catalyzes the oxidation of succinate to fumarate, transferring electrons to ubiquinone (coenzyme Q10) in the process.

Pathophysiology

Complex II deficiency disrupts the electron transport chain, leading to impaired ATP production and an accumulation of metabolic intermediates. This can result in a wide range of clinical manifestations, depending on the severity of the deficiency and the tissues affected.

The deficiency is often caused by mutations in the genes encoding the subunits of Complex II, such as SDHA, SDHB, SDHC, and SDHD. These mutations can lead to a loss of function or reduced activity of the enzyme complex.

Clinical Manifestations

The symptoms of Complex II deficiency can vary widely but often include:

• Neurological symptoms: Developmental delay, hypotonia, seizures, and ataxia.
• Muscle weakness: Myopathy and exercise intolerance.
• Cardiomyopathy: Heart muscle weakness leading to heart failure.
• Metabolic acidosis: Due to the accumulation of lactic acid and other metabolites.

Diagnosis

Diagnosis of Complex II deficiency typically involves a combination of clinical evaluation, biochemical testing, and genetic analysis. Key diagnostic steps include:

• Biochemical assays: Measurement of enzyme activity in muscle biopsies or cultured fibroblasts.
• Genetic testing: Identification of mutations in the SDH genes.
• Imaging studies: MRI or CT scans to assess brain and muscle involvement.

Treatment

Currently, there is no cure for Complex II deficiency, and treatment is primarily supportive and symptomatic. Management strategies may include:

• Nutritional support: High-calorie diets to meet energy demands.
• Cofactor supplementation: Use of riboflavin (vitamin B2) and coenzyme Q10 to support mitochondrial function.
• Physical therapy: To maintain muscle strength and function.
• Management of complications: Such as anticonvulsants for seizures and medications for heart failure.

Prognosis

The prognosis for individuals with Complex II deficiency varies depending on the severity of the condition and the organs involved. Early diagnosis and supportive care can improve quality of life and outcomes for affected individuals.

Also see

• Mitochondrial disease
• Oxidative phosphorylation
• Succinate dehydrogenase
• Genetic disorders