combined oxidative phosphorylation deficiency 37

Combined oxidative phosphorylation deficiency 37 is a multisystem disorder that primarily affects energy production in the body, with significant involvement of the central nervous system. The condition is caused by pathogenic variants in the MICOS13 gene, which plays a vital role in maintaining mitochondrial structure and function. It generally presents in infancy with early developmental challenges and multiple systemic complications. Precise prevalence estimates are not well established, and the disorder is inherited in an autosomal recessive pattern.

Individuals with combined oxidative phosphorylation deficiency 37 exhibit a complex clinical picture characterized by constant features such as poor head control, persistent head lag, and hypotonia. Neurologically, there is global developmental delay, progressive neurologic deterioration, and reduced eye contact, accompanied by visual impairment and optic atrophy that reflect central nervous system involvement. Additional systemic findings include hypothermia, feeding difficulties, respiratory failure and insufficiency, metabolic disturbances such as lactic acidosis and hyperalaninemia, as well as hepatic manifestations like hypoalbuminemia and macrovesicular hepatic steatosis. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the MICOS13 gene. The MICOS13 protein is essential for the maintenance of mitochondrial structure and efficient energy production, and its disruption leads to widespread cellular dysfunction. Combined oxidative phosphorylation deficiency 37 is inherited in an autosomal recessive manner, meaning that an affected individual has received one mutated copy of the gene from each parent. Genetic counseling is recommended for families to understand the recurrence risks and implications for family planning.

Currently, management focuses on supportive care and symptom management as no specific treatments have been approved for combined oxidative phosphorylation deficiency 37. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the diverse needs including motor support, nutritional interventions, and respiratory care. Regular surveillance is an essential part of long-term care, helping to identify and manage emerging complications before they become serious. Patients should discuss treatment options with their healthcare team and seek genetic counseling for further guidance.

The prognosis for individuals with combined oxidative phosphorylation deficiency 37 is highly variable, with outcomes affected by the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, interventions aimed at managing complications can lead to periods of stabilization, although the condition may progress in some individuals. Severity and symptoms vary widely between individuals. Families often find it helpful to connect with specialists familiar with this condition, as well as genetic counselors, to obtain personalized care recommendations.