Mitochondrial Complex IV Deficiency / Leigh Syndrome (COX10)
Pathogenic variants in the gene COX10 cause autosomal recessive mitochondrial disorders resulting from deficiency in mitochondrial complex IV.
- Mitochondrial complex IV deficiency has variable onset and severity. Some individuals experience infantile onset with acute neurometabolic decompensation and hypertrophic cardiomyopathy, and exhibit a rapidly progressive clinical course that can include encephalopathy and respiratory depression. Other individuals present with subtle neurological signs beginning later in life. Neurological deficiencies include loss of developmental milestones, including the ability to walk, sit, or speak, seizures, and spastic weakness in all extremities. Life expectancy is reduced.
- Leigh syndrome due to mitochondrial COX4 deficiency is typically an early-onset progressive neurodegenerative disorder. Clinical manifestations include failure to thrive, severe developmental delay, anemia, hypotrophy, hypotonia, lactic acidosis, and sensorineural deafness. Life expectancy can be reduced.
No genotype/phenotype correlations have been documented.
For information about carrier frequency and residual risk, please see the residual risk table.