combined oxidative phosphorylation defect type 24

Combined oxidative phosphorylation defect type 24 is a condition affecting energy production in cells due to abnormalities in mitochondrial function. It is caused by mutations in the NARS2 gene, which plays a key role in protein synthesis within mitochondria. This condition is inherited in an autosomal recessive pattern and is very rare, affecting fewer than 1 in 1,000,000 people. Individuals with the disorder may present symptoms in early childhood, although the severity and range of manifestations can vary substantially.

Characteristic findings in this condition include the consistent presence of ragged-red muscle fibers and decreased activity of both mitochondrial complex IV and complex I, findings that are considered obligate features. Patients may also experience skeletal muscle atrophy, easy fatigability, dysarthria, seizures, ptosis, elevated circulating creatine kinase, proximal muscle weakness, and mild intellectual disability, along with weakness of facial musculature. Not all individuals experience all of these features, and the severity varies considerably. Although some cognitive challenges are noted, there is no distinct phase of developmental regression reported.

This condition is caused by mutations in the NARS2 gene, which is essential for proper mitochondrial protein synthesis and energy production. It is inherited in an autosomal recessive manner, meaning that an affected individual has received one mutated copy of the gene from each parent. Because the disorder is very rare, it is more common when parents share a common ancestor, increasing the likelihood that both carry the same rare mutation. Families are advised to pursue genetic counseling to understand the recurrence risk and implications for future family planning.

Currently, management focuses on supportive care and symptom management since there are no established foundational therapies or FDA-approved treatments for this condition. A multidisciplinary team approach, involving specialists experienced in mitochondrial disorders, is recommended to address the range of symptoms including neuromuscular and cognitive challenges. Regular surveillance is an essential part of long-term care, as ongoing monitoring can help identify and manage potential complications early. Patients should discuss treatment options with their healthcare team and consider genetic counseling to guide family planning and overall management.

The course of combined oxidative phosphorylation defect type 24 is highly variable, with outcomes differing based on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals are able to lead fulfilling lives despite the challenges posed by the condition. Outcomes described in medical literature continue to evolve as standards of care improve, and severity and symptoms vary widely between individuals. It is recommended that families connect with specialists and genetic counselors for ongoing support and to explore management options tailored to their specific needs.