Abstract
Mitochondrial illnesses are a broad, diverse group of molecular disorders affecting the mitochondrial electron transport chain. Mitochondrial complex IV deficiency nuclear type 1 (MC4DN1) or cytochrome c oxidase (COX) deficiency is an autosomal recessive condition portrayed by encephalopathy and hasty neurodegeneration with cognitive and motor deficits between the age of 6 and 18 months after initial growth (Abdulhag et al. 2015). COX deficiency is attributable to a lack of a COX enzyme with varied clinical symptoms, encompassing isolated myopathy, and may range from a severe multisystem disease affecting multiple tissues and organs (Alston et al. 2017). Clinical attributes include fatal hypertrophic cardiomyopathy (may result in neonatal death), megalohepatia, liver dysfunction, myasthenia, decreased ability to perform physical exercise, intellectual disability, and delay in acquiring motor skills (Rak et al. 2016). Mitochondrial complex IV is the terminal enzyme of the electron transport chain, which exists as a dimer and consists of 13 polypeptide subunits. Of the 13 monomer subunits, three units designated as COX1, COX2, and COX3 are encoded by the mitochondrial genome and form the enzyme’s essential catalytic subunits that perform the role of electron transport (Abdulhag et al. 2015). Biogenesis and assembly of complex IV depend on many extraneous factors, including nuclear copper encoded chaperone. Much of the isolated COX defects are associated with mutations in these extraneous factors. Particularly, disease-causing mutations have been identified in genes encoding SURF1 (critical for the formation of early assembly substrates); SCO1, 2 (required for the incorporation of the copper moiety into complex); COX10, 15 (essential for heme A biosynthesis); TACO1; and LRPPRC (necessary for COX expression) (Abdulhag et al. 2015). COX deficiency is mostly attributed to mutations occurring in nuclear-coded assembly factors and occasionally to mutations occurring in structural subunits. Also, pathogenic mutations that induce COX deficit are commonly found in nuclear DNA and are linked with autosomal recessive inheritance, whereas rare COX deficiency is associated with mutations in the mitochondrial-encoded DNA gene that indicates parental inheritance. The disease primarily targets the skeletal muscles, but it can be extended and impacts the brain, heart, kidney, and liver (Abdulhag et al. 2015; Alston et al. 2017; Rak et al. 2016).
References
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Jamwal, S., Gautam, A. (2024). Mitochondrial Complex IV Deficiency, Nuclear (MC4DN) Types 1–24. In: Rezaei, N. (eds) Genetic Syndromes. Springer, Cham. https://doi.org/10.1007/978-3-319-66816-1_424-1
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DOI: https://doi.org/10.1007/978-3-319-66816-1_424-1
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