Combined oxidative phosphorylation defect type 2

Combined oxidative phosphorylation deficiency type 2 (COXPD2) is an extremely rare mitochondrial disorder caused by mutations in the MRPS16 gene, which encodes a protein component of the mitochondrial ribosomal small subunit. This protein is essential for the translation of mitochondrial DNA-encoded proteins that form critical subunits of the oxidative phosphorylation (OXPHOS) complexes. When MRPS16 is deficient, the mitochondrial ribosome cannot properly synthesize these proteins, leading to combined deficiencies of multiple respiratory chain complexes and severely impaired cellular energy production. The disease presents in the neonatal period with a severe, rapidly progressive clinical course. Key features include lactic acidosis, agenesis of the corpus callosum, dysmorphic facial features, and fatal encephalopathy. Affected infants typically show profound neurological impairment, hypotonia, and metabolic crisis shortly after birth. Additional findings may include edema and liver dysfunction. The condition affects primarily the central nervous system and metabolic homeostasis, reflecting the high energy demands of the developing brain. There is currently no curative treatment for COXPD2. Management is supportive and symptomatic, focusing on metabolic stabilization and comfort care. The prognosis is extremely poor, with reported cases resulting in early neonatal or infantile death. Genetic counseling is recommended for affected families, as the condition follows an autosomal recessive inheritance pattern. Prenatal or preimplantation genetic testing may be available for families with a known pathogenic variant.

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