combined oxidative phosphorylation defect type 25

Combined oxidative phosphorylation defect type 25 is a condition in which the body’s ability to produce energy is impaired due to a mutation in the MARS2 gene. This disorder affects multiple organ systems, with prominent involvement of the nervous system and features that impact facial structure, muscle tone, and growth. It is inherited in an autosomal recessive pattern, meaning that affected individuals receive a mutated copy of the gene from each parent. The condition is extremely rare, affecting fewer than 1 in 1,000,000 people.

Individuals with combined oxidative phosphorylation defect type 25 typically exhibit a constellation of features that impact several body systems. Characteristic findings include facial dysmorphisms such as anteverted nares, a short nose, depressed nasal bridge, low-set ears, and a long philtrum. Neurologically, affected children experience global developmental delay and, along with generalized hypotonia, may show signs of cerebellar atrophy. Additionally, many individuals present with feeding difficulties, reduced circulating growth hormone concentration, and respiratory complications such as aspiration pneumonia. Other features that occur in a subset of patients include smooth philtrum, hypoplasia of the pons, failure to thrive, wide nasal bridge, prominent forehead, chronic constipation, hypertelorism, ventriculomegaly, cerebral atrophy, intraventricular hemorrhage, and syndactyly. Not all individuals experience all these features, and severity varies considerably.

The condition is caused by a mutation in the MARS2 gene, which plays a crucial role in mitochondrial function and energy production. It is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for a child to be affected. This inheritance pattern means that each sibling of an affected individual has a 25% chance of being affected. The condition is particularly more common in families where parents share a common ancestor, as this increases the likelihood of both carrying the same rare genetic variant. Genetic counseling is recommended for families to better understand the risks and implications for future pregnancies.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to the individual’s needs. Because no treatments have been specifically approved for combined oxidative phosphorylation defect type 25, care typically involves a multidisciplinary team that may include specialists in neurology, nutrition, respiratory therapy, and developmental pediatrics. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Genetic counseling is also recommended so that families can explore reproductive options and receive guidance on managing the condition.

The long-term outlook for individuals with combined oxidative phosphorylation defect type 25 is variable, with outcomes that depend on the severity of symptoms, age at diagnosis, and access to specialized care. As is true with many multisystem conditions, some individuals may experience periods of relative stabilization while others might face ongoing challenges related to feeding, growth, and respiratory function. Outcomes described in medical literature continue to evolve as standards of care improve, and many families benefit from regular monitoring and comprehensive supportive services. Connecting with specialists familiar with the condition, genetic counselors, and patient support groups can provide valuable guidance as well as up-to-date information on management options.