SNP Shot: Genomic Insights

Cytochrome c oxidase (COX) deficiency is a genetic disorder impacting various organs, such as skeletal muscles, heart, brain, and liver. Symptoms usually manifest before age 2, but can emerge later in milder cases.

The severity of COX deficiency varies considerably, even within the same family. Mildly affected individuals often exhibit muscle weakness (myopathy) and reduced muscle tone (hypotonia) without other complications. Severely affected individuals experience multi-system problems, often including severe brain dysfunction (encephalomyopathy). Around 25% develop hypertrophic cardiomyopathy, a condition where the heart muscle enlarges and weakens. An enlarged liver (hepatomegaly) is another potential symptom, potentially leading to liver failure. Many individuals with COX deficiency experience lactic acidosis, a buildup of lactic acid that can cause nausea, irregular heartbeat, and can be life-threatening.

A significant number of individuals with COX deficiency present with a specific set of characteristics known as Leigh syndrome. Symptoms of Leigh syndrome include cognitive decline, motor difficulties, hypertrophic cardiomyopathy, feeding issues, and brain abnormalities. COX deficiency is one of several causes of Leigh syndrome.

The prognosis for individuals with COX deficiency varies. Many do not survive beyond childhood, while those with milder symptoms may live into adolescence or adulthood.

Inheritance:

The inheritance pattern of COX deficiency depends on the affected gene. When caused by mutations in nuclear DNA genes, it follows an autosomal recessive pattern. This means both copies of the gene in each cell must have mutations. Parents of individuals with autosomal recessive conditions each carry one copy of the mutated gene but usually do not exhibit symptoms. When mutations occur in mitochondrial DNA (mtDNA) genes, the condition is inherited maternally. This pattern affects genes in mtDNA. Because mitochondria are passed from mother to child through the egg cell, only mothers can transmit mtDNA mutations. These disorders can occur in every generation and affect both males and females, but fathers cannot pass mtDNA-related traits to their children.