Lethal neonatal mitochondrial phenotype caused by a novel polymerase subunit gamma mutation A case report

Rationale: Polymerase subunit gamma (POLG) is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, which is involved in the replication of mitochondrial DNA. Mutations in these genes are associated with a range of clinical syndromes characterized by secondary mtDNA defect including mtDNA mutation and mtDNA depletion which may culminate in complete failure of energy production (respiratory changes complex 1 defect) as in this case. Patient concerns: We herein report a full term Saudi female neonate born to consanguineous parents, who was noticed immediately after birth to have severe hypotonia, poor respiratory effort, and dysmorphic features. She had 3 siblings who died with same clinical scenario in neonatal period. Diagnoses: Molecular genetic testing revealed a novel compound heterozygous mutation of POLG gene c.680G>A (p.Arg227Gin) and c.3098C>T (p.Ala1033Val). Interventions: The patient remained in neonatal intensive care unit with multidisciplinary team management and was ventilator dependent until she passed away. Outcomes: The detected mutation had led to complete failure of energy production (respiratory changes complex 1 defect) until she died at the age of 5 months. Lessons: Mitochondrial respiratory chain defect should be considered in patients with severe neonatal hypotonia, encephalopathy, and respiratory failure especially in highly consanguineous population.