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Fatal infantile liver failure associated with mitochondrial DNA depletion
M R Mazziotta1, E Ricci, E Bertini
1Department of Metabolism, Bambino Gesù Hospital, Rome, Italy.
Insights
This study reports a fatal case of infantile liver failure due to mitochondrial DNA depletion, characterized by severe metabolic acidosis and respiratory chain defects. This highlights the importance of considering mitochondrial DNA depletion in infants with unexplained liver failure and myopathy.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Mitochondrial DNA depletion syndrome (MDDS) is a group of inherited metabolic disorders.
- It is characterized by a significant reduction in mitochondrial DNA (mtDNA) copy number in affected tissues.
- MDDS can lead to a variety of clinical manifestations, including myopathy, liver disease, and neurological dysfunction.
Observation:
- A 3-month-old infant presented with hypotonia, vomiting, severe metabolic acidosis, and abnormal liver function.
- The infant developed hepatomegaly and rapidly progressive liver failure, leading to death at 4 months of age.
- Autopsy revealed a fatty liver with lipid droplet accumulation in hepatocytes.
Findings:
- Marked decrease in respiratory chain enzymes encoded by mtDNA in the liver (90% depletion of mtDNA) and partial decrease in muscle (53% depletion).
- Other tissues showed normal mtDNA levels and enzyme activity.
- This is the second reported case of fatal infantile liver failure linked to mtDNA depletion.
Implications:
- Mitochondrial DNA depletion should be considered in the differential diagnosis of infants presenting with unexplained liver failure, particularly when accompanied by multiple respiratory chain defects.
- Variable tissue expression of mtDNA depletion can complicate diagnosis.
- Early recognition and diagnosis are crucial for potential management strategies in affected families.
Abstract:
A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.