combined oxidative phosphorylation deficiency 36

Combined oxidative phosphorylation deficiency 36, also known as COXPD36, is a multisystem metabolic disorder affecting energy production in cells. The condition results from pathogenic variants in the MRPS2 gene, which plays a critical role in mitochondrial protein synthesis. Affected individuals typically present in early childhood with neurological and metabolic abnormalities, including intellectual disability, global developmental delay, and increased circulating lactate. Although specific prevalence estimates are not available, the autosomal recessive inheritance pattern suggests that it is an uncommon condition.

The clinical presentation of combined oxidative phosphorylation deficiency 36 is marked by a consistent constellation of symptoms. Neurologically, nearly all affected individuals experience intellectual disability, poor speech, and global developmental delay, underscoring the cognitive impact of the disorder. Metabolic findings such as increased circulating lactate and hypoglycemia are always present, while hypotonia further contributes to motor challenges. In addition, sensorineural hearing impairment is a characteristic feature. A number of other signs, observed in a subset of individuals, include upslanted palpebral fissures, elevated liver enzymes, hyperalaninemia, headache, exodeviation, low-set ears, premature skin wrinkling, failure to thrive, exercise intolerance, lower limb muscle weakness, and myalgia. Not all individuals experience all features, and severity varies considerably.

Combined oxidative phosphorylation deficiency 36 is caused by pathogenic variants in the MRPS2 gene. MRPS2 is responsible for encoding a protein that is essential for mitochondrial ribosome function and, consequently, for effective oxidative phosphorylation. The condition is inherited in an autosomal recessive manner, meaning that an affected individual has received one altered copy of the gene from each parent. Families are advised to seek genetic counseling to better understand the implications for current and future family planning.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to the individual. Although there are no specific foundational therapies or approved treatments linked to this condition, a multidisciplinary approach is essential. Patients typically benefit from regular surveillance to monitor metabolic parameters and developmental progress as part of long-term care. In addition, genetic counseling is recommended to help families navigate treatment options and to plan for future care. The involvement of specialists in neurology, metabolic disorders, and developmental pediatrics can be crucial in ensuring comprehensive care.

The outlook for individuals with combined oxidative phosphorylation deficiency 36 is highly variable, with outcomes depending on the severity of symptoms, age at diagnosis, and access to specialized care. Many individuals continue to live into adulthood with supportive care, although cognitive and developmental challenges persist. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists and genetic counselors, and to consider support groups or expert centers for ongoing guidance.