cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 is a severe multisystem condition that primarily affects infants, usually presenting in the first few months of life. The disorder is caused by pathogenic variants in the SCO2 gene, a critical gene involved in the function of the mitochondrial cytochrome c oxidase complex essential for cellular energy production. Affected infants typically present with both neurologic and cardiac symptoms, underscoring its dual impact on the brain and heart. As no precise birth prevalence data is available, the condition is understood to be extremely rare and represents one of the more severe mitochondrial disorders.

The clinical presentation of this condition is characterized by a constellation of findings that affect multiple organ systems. Neurologically, affected infants exhibit diffuse white matter abnormalities, abnormal brainstem MRI signal intensity, cerebellar vermis atrophy, and encephalopathy, all of which contribute to a profound impact on central nervous system function. Craniofacial features such as low-set ears and a wide nasal bridge are consistently observed. In addition, neuromuscular involvement is evident through mixed demyelinating and axonal polyneuropathy, muscle weakness, upper limb hypertonia, and a tremor, while abnormal gait patterns such as a steppage gait and the presence of pes cavus may be noted as part of the evolving clinical course. Cardiac involvement is marked by cardiomegaly, and systemic features include failure to thrive, lacticaciduria, and an increased risk of malignant hyperthermia. Not all individuals experience every feature, and severity varies considerably between patients.

The underlying cause of cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 is genetic, resulting from mutations in the SCO2 gene. SCO2 plays a pivotal role in the assembly and function of the cytochrome c oxidase complex within mitochondria, and disruptions in its function lead to impaired cellular energy production. This condition follows an autosomal recessive inheritance pattern, meaning that an affected child inherits two mutated copies of the SCO2 gene—one from each parent. Families with a common ancestor may have a higher likelihood of both parents carrying the same rare mutation, which underscores the importance of genetic counseling for family planning.

Currently, management of cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 focuses primarily on supportive care and symptom management, as no FDA-approved therapies are available at this time. Treatment is highly individualized and typically involves a multidisciplinary team that may include neurologists, cardiologists, metabolic specialists, and physical therapists. Regular monitoring is an essential component of long-term management, with ongoing surveillance to detect potential complications early. This multidisciplinary approach ensures that care is coordinated across various specialties, and families are advised to engage with specialists experienced in managing complex mitochondrial disorders. Genetic counseling is also recommended to help families understand the inheritance pattern and guide future family planning.

The outlook for individuals with this condition remains challenging, and the course is highly variable between affected infants. In many cases, the severity of symptoms, particularly those involving the heart and brain, impacts overall outcomes. With current standards of supportive care and careful monitoring, some aspects of the condition may be stabilized for a period; however, the overall prognosis remains poor. Outcomes described in medical literature continue to evolve as standards of care improve, and ongoing advances in multidisciplinary approaches may provide incremental benefits in patient management. Families are encouraged to connect with genetic counselors, specialist care teams, and patient support networks to discuss future care options and to receive guidance throughout the management process.