cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 is a severe, multi-system disorder characterized by early-onset heart and brain involvement. It is caused by pathogenic variants in the COX15 gene, which impair the function of cytochrome c oxidase, a key enzyme in cellular energy production. Affected infants present with a constellation of symptoms affecting the nervous, cardiac, ophthalmologic, and gastrointestinal systems. Precise prevalence estimates are not well established, and the condition typically manifests in early infancy with devastating consequences.

Clinically, affected infants exhibit a range of systemic manifestations. Neurologically, they show hypotonia, motor regression, and lower limb spasticity. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Cardiac involvement is evident with hypertrophic cardiomyopathy, while neuroimaging reveals bilateral basal ganglia lesions. Ophthalmologic signs such as retinopathy and horizontal nystagmus are present, and gastrointestinal disturbances appear as bloody diarrhea. Additional features including feeding difficulties, lactic acidosis, and midface retrusion contribute to the complex clinical picture. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the COX15 gene, which plays an essential role in the assembly and function of cytochrome c oxidase, a critical component of the mitochondrial electron transport chain responsible for energy production. It is inherited in an autosomal recessive pattern, meaning that an affected child inherits a mutation from each parent, who are typically asymptomatic carriers. Families are advised to seek genetic counseling for a detailed discussion of recurrence risks and family planning options.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Treatment is tailored to each affected child by a multidisciplinary team and involves regular surveillance to monitor the function of the heart, nervous system, and other affected organs. In addition to addressing acute symptoms, ongoing monitoring helps detect complications early when intervention may be most effective. Families are encouraged to work closely with their healthcare team, including specialists in cardiology, neurology, and supportive care services, and to consider genetic counseling for further guidance.

The outlook for children affected by this condition is highly variable, with outcomes depending on the severity of symptoms, the timing of diagnosis, and access to specialized care. Many affected children experience an initial phase of developmental regression followed by a period of relative stabilization, although some may later face further motor decline. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling to better understand the implications for long-term care and family planning.