Living donor liver transplantation in a pediatric patient with mitochondrial DNA depletion syndrome caused by two novel POLG1 mutations: a case report and literature review.

BACKGROUND: Mitochondrial DNA depletion syndrome (mtDDS) is a rare genetic disorder caused by mutations in nuclear genes responsible for mitochondrial DNA maintenance, most notably POLG1. The disease is characterized by diverse clinical manifestations, including myopathy, hepatopathy, and neurological deficits. Due to its phenotypic heterogeneity, diagnosing mtDDS in pediatric populations remains a significant clinical challenge, often leading to delays in life-saving interventions.

CASE DESCRIPTION: We report the case of an 11-month-old male infant presenting with acute liver failure and recurrent hypoglycemia. Laboratory findings revealed elevated liver enzymes, jaundice, and persistent metabolic distress. Notably, the patient lacked the neurological symptoms typically associated with POLG1 mutations, complicating the initial clinical picture. Genetic analysis via whole exome sequencing (WES) identified two novel compound heterozygous mutations in the POLG1 gene (695G>A and 1735C>T), confirming the diagnosis of mtDDS. Following the diagnosis, the patient underwent a successful liver transplantation, which resulted in significant clinical stabilization and improved quality of life.

CONCLUSIONS: This case expands the known mutational spectrum of the POLG1 gene and highlights an atypical presentation of mtDDS isolated to hepatic dysfunction. Our findings underscore the critical importance of early genetic testing, such as WES, in infants with unexplained liver failure or metabolic crises. Timely diagnosis is essential to guide surgical interventions like liver transplantation, which can effectively improve outcomes. Clinicians should maintain a high index of suspicion for underlying mitochondrial genetic defects in pediatric hepatopathy to facilitate early intervention and long-term management.