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

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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.


Molecular genetic testing revealed a novel compound heterozygous mutation of POLG gene c.680G>A (p.Arg227Gin) and c.3098C>T (p.Ala1033Val).


The patient remained in neonatal intensive care unit with multidisciplinary team management and was ventilator dependent until she passed away.


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.


Mitochondrial respiratory chain defect should be considered in patients with severe neonatal hypotonia,encephalopathy, and respiratory failure especially in highly consanguineous population.

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