combined oxidative phosphorylation defect type 7

Combined oxidative phosphorylation defect type 7 is a rare mitochondrial condition that affects energy production in cells, particularly impacting the nervous system and muscles. It is caused by alterations in the MTRFR gene, which plays a role in mitochondrial protein synthesis. The disorder typically presents in infancy or early childhood, with affected children initially developing normally before symptoms emerge. The condition is very rare, affecting fewer than 1 in a million people, and its progression can be variable.

After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Characteristic clinical features include global developmental delay, increased circulating lactate levels, and prominent ocular findings such as optic atrophy, nystagmus, and ptosis. Many children also develop facial diplegia, ataxia, and areflexia, while additional features like dysphagia, dysarthria, and reduced mastication may be observed in some cases. Not all individuals experience all features, and severity varies considerably, with differences in both cognitive and neurological presentations across affected individuals.

The underlying cause of combined oxidative phosphorylation defect type 7 is a defect in the MTRFR gene, which is essential for proper mitochondrial protein synthesis. This disruption impairs the cell’s ability to generate energy efficiently, particularly affecting high-energy systems such as the brain and muscles. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited two copies of the altered gene, one from each parent. Families with a shared common ancestry may have an increased likelihood of both parents carrying the same rare genetic change, and genetic counseling is recommended to discuss recurrence risks and family planning options. Associated genes include MTRFR.