SNP Shot: Genomic Insights

Mitochondrial complex III deficiency is a genetic disorder impacting various organs, including the brain, kidneys, liver, heart, and skeletal muscles. The condition's symptoms typically manifest during infancy, although they can emerge later in life.

The severity of mitochondrial complex III deficiency differs significantly among individuals. Those with milder cases often experience muscle weakness (myopathy) and pronounced fatigue, especially during physical activity (exercise intolerance). Individuals with more severe forms may encounter issues affecting multiple organ systems. These can include liver disease potentially leading to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy may result in delayed psychomotor development, movement disorders, decreased muscle tone (hypotonia), and impaired communication skills. Cardiomyopathy, a type of heart disease, may also occur, potentially progressing to heart failure.

Lactic acidosis, characterized by a buildup of lactic acid, is common in individuals with mitochondrial complex III deficiency. Some may also experience ketoacidosis (ketone buildup) or hyperglycemia (elevated blood glucose). Dangerously high levels of these substances can be life-threatening.

Mitochondrial complex III deficiency can be fatal during childhood. However, those with milder symptoms may survive into adolescence or adulthood.

Inheritance:

Mitochondrial complex III deficiency typically follows an autosomal recessive inheritance pattern. This means that both copies of the relevant gene in each cell must carry mutations for the condition to develop. The parents of an individual with an autosomal recessive disorder each carry one copy of the mutated gene but usually do not exhibit any symptoms. In some instances, mutations in the MT-CYB gene can cause the condition. These mutations are not inherited, but rather arise spontaneously in individuals with no family history of the disorder. Other instances of mutations in the MT-CYB gene are inherited through a mitochondrial inheritance pattern (maternal inheritance). Mitochondrial inheritance pertains to genes found in mtDNA. Because developing embryos inherit mitochondria solely from egg cells (not sperm cells), children can only inherit mtDNA mutations from their mother. These conditions can appear across generations and affect both males and females. However, fathers cannot transmit mtDNA-related traits to their offspring.