Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (COXPD3) is an extremely rare and severe mitochondrial disorder caused by mutations in the TSFM gene, which encodes the mitochondrial translation elongation factor Ts (EF-Ts). This protein is essential for mitochondrial protein synthesis, and its deficiency leads to impaired assembly and function of multiple oxidative phosphorylation (OXPHOS) enzyme complexes, particularly complexes I, III, and IV. The disease results in a profound energy deficit in tissues with high metabolic demands, including the brain, heart, liver, and skeletal muscle. Clinical presentation typically begins in the neonatal or early infantile period and is characterized by severe encephalomyopathy or hypertrophic cardiomyopathy, or a combination of both. Affected infants may present with lactic acidosis, hypotonia, developmental regression, seizures, feeding difficulties, and progressive neurological deterioration. Some patients exhibit features consistent with Leigh syndrome on brain imaging. The cardiac involvement can include severe hypertrophic cardiomyopathy leading to heart failure. The disease course is typically rapidly progressive and fatal in infancy or early childhood. There is currently no curative treatment for COXPD3. Management is supportive and symptomatic, focusing on nutritional support, management of seizures, cardiac monitoring, and palliative care. Cofactor supplementation and mitochondrial cocktails (such as coenzyme Q10, riboflavin, and carnitine) have been tried in some cases, though evidence of efficacy is limited. Genetic counseling is important for affected families.

Common questions about Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3