combined oxidative phosphorylation deficiency 51

Combined oxidative phosphorylation deficiency 51 (COXPD51) is a complex multisystem condition that primarily affects energy production in the body. It is caused by variants in the PTCD3 gene, which plays a crucial role in mitochondrial function. The condition typically manifests in infancy or early childhood with significant impacts on growth, neurological function, and respiratory status. Precise prevalence estimates are not well established for this disorder.

The clinical presentation of COXPD51 is marked by a constellation of findings affecting multiple organ systems. Neurologically, individuals exhibit cerebral atrophy, nystagmus, optic atrophy, myoclonus, and rigidity. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, underscoring the profound impact on cognitive and motor abilities. In addition, children present with severe short stature, growth delay, small size for gestational age, and intrauterine growth retardation, while respiratory difficulties such as neonatal respiratory distress, respiratory failure, and aspiration pneumonia are consistently observed. Hearing impairment and the need for nasogastric tube feeding further highlight the multisystem involvement. Not all individuals experience every feature, and severity varies considerably.

COXPD51 is caused by pathogenic variants in the PTCD3 gene, which is essential for proper mitochondrial function and energy production. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited one altered copy of the gene from each parent. This inheritance pattern implies that both parents are carriers, and each child has a 25% chance of being affected when both parents carry a pathogenic variant. Genetic counseling is recommended to help families understand the implications and recurrence risks associated with the condition.

Currently, management focuses on supportive care and symptom management, as no treatments are specifically approved for COXPD51. Treatment is highly individualized and typically involves a multidisciplinary team that may include neurologists, respiratory specialists, nutritionists, and other experts. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Families are encouraged to discuss treatment options with their healthcare team and to seek genetic counseling for further guidance on managing the condition.

COXPD51 is a lifelong neurodevelopmental condition characterized by an initial phase of developmental regression, followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes depend on many factors including the age at diagnosis, the severity of symptoms, and access to specialized care. That severity and symptoms vary widely between individuals, and modern improvements in supportive care continue to influence long-term outcomes. Families often find it helpful to connect with genetic counselors and experts familiar with this condition for ongoing support and guidance.