combined oxidative phosphorylation deficiency 57

Combined oxidative phosphorylation deficiency 57 is a mitochondrial disorder characterized by impaired energy production affecting several organ systems, especially the central nervous system. It is linked to pathogenic variants in the CRLS1 gene, which plays a critical role in maintaining normal mitochondrial function. The condition typically presents in early childhood with features such as global developmental delay and cognitive difficulties. As an autosomal recessive disorder, its occurrence is rare and precise prevalence estimates are not well established.

Characteristic clinical features include decreased activity of mitochondrial complexes I, III, and IV, which are invariably present, and a marked global developmental delay. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Neurological manifestations such as hypotonia, myoclonus, and dystonia are observed, along with variable findings including cerebral atrophy, bull's eye maculopathy, and occasional seizure activity. Not all individuals experience all features, and severity varies considerably.

Combined oxidative phosphorylation deficiency 57 is caused by pathogenic variants in the CRLS1 gene, which is essential for the synthesis of cardiolipin—an important lipid for mitochondrial membrane integrity and function. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual inherits two copies of the altered gene, one from each parent. This genetic basis highlights the importance of genetic counseling for families to understand recurrence risks and discuss family planning options.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. A multidisciplinary team, including specialists in neurology and metabolic disorders, is essential for addressing the complex and variable clinical manifestations. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Families should discuss treatment options with their healthcare team and consider genetic counseling to tailor management strategies to each individual’s needs.

Combined oxidative phosphorylation deficiency 57 is a lifelong condition characterized by an initial phase of developmental regression followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care, and the clinical course can be highly variable. Outcomes described in medical literature continue to evolve as standards of care improve. Connecting with a genetic counselor can provide guidance for families, and support groups may offer valuable resources.