Mitochondrial DNA depletion syndrome causing liver failure

Area of Science:

• Pediatric Hepatology
• Mitochondrial Genetics
• Rare Diseases

Background:

• Mitochondrial DNA (mtDNA) depletion syndromes are genetic disorders affecting mtDNA maintenance.
• These syndromes present with diverse clinical manifestations, notably fulminant liver failure.

Observation:

• Two infants presented with severe, fatal hepatopathy.
• Key clinical indicators included elevated serum lactate and a positive family history in one case.
• Other potential causes of acute liver failure were systematically excluded.

Findings:

• Case 1 revealed a homozygous mutation (c.3286C>T, p.Arg1096Cys) in the POLG gene.
• Case 2 exhibited compound heterozygous mutations in the MPV17 gene: a novel c.408T>G (p.Tyr136X) and a previously reported c.293C>T (p.Pro98Leu).

Implications:

• Mitochondrial DNA depletion syndrome is a critical, albeit rare, etiology of acute liver failure in pediatric patients.
• Genetic identification of causative mutations is crucial for diagnosis and potential therapeutic strategies.
• This study highlights the importance of considering mtDNA depletion syndromes in infants with unexplained severe liver disease.