cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 is a severe disorder that primarily affects the heart and brain of infants. It is caused by mutations in the COA6 gene, which is critical for the proper function of mitochondrial complex IV. The condition manifests early in life with significant cardiac, metabolic, and neurological involvement. Because prevalence estimates are not well established, detailed data on occurrence are limited.

The clinical presentation is marked by consistent findings that include hypothermia, reduced left ventricular ejection fraction, tricuspid regurgitation, hypertrophic cardiomyopathy, aortic regurgitation, and left ventricular noncompaction. Affected infants often experience patent ductus arteriosus and tachypnea, along with metabolic disturbances such as lactic acidosis and metabolic acidosis. Neurological features include neonatal hypotonia and a short chin. Not all individuals may exhibit every feature to the same extent, and the severity of symptoms can vary considerably.

This condition is caused by mutations in the COA6 gene, which encodes a protein essential for the activity of mitochondrial complex IV. It is inherited in an autosomal recessive pattern, meaning that an affected child receives one mutated copy of the gene from each parent. In families where parents share a common ancestor, the likelihood of both carrying the mutation is increased. Genetic counseling is recommended to help families understand the recurrence risks and the implications for future pregnancies.

Currently, management focuses on supportive care and symptom management since there are no FDA-approved or foundational therapies available for this condition. Treatment is tailored to address the specific cardiac, metabolic, and neurological challenges, and is typically provided by a multidisciplinary team. Regular surveillance, including cardiac monitoring and metabolic assessments, is an essential part of long-term care. Patients and families are encouraged to discuss treatment options and supportive strategies with their healthcare team, and genetic counseling is recommended to understand the condition and future reproductive options.

The outlook for individuals with this condition remains challenging and varies depending on the severity of symptoms and the timely implementation of supportive care. While the disease is characterized by an early and severe presentation, outcomes described in medical literature continue to evolve as standards of care improve. With current management, some individuals may experience a period of relative stabilization after the initial presentation. Families are encouraged to connect with specialists and genetic counselors to obtain personalized guidance and support, acknowledging that ongoing research may lead to further improvements in care.