Mitochondrial DNA depletion in children

Area of Science:

• Genetics
• Pediatrics
• Biochemistry

Background:

• Mitochondrial DNA (mtDNA) depletion is a group of genetic disorders characterized by reduced levels of mtDNA.
• These disorders can lead to severe multi-systemic complications, particularly affecting high-energy-demand organs like the brain, liver, and muscles.

Observation:

• Two unrelated infants presented with failure to thrive, hypotonia, hepatomegaly, hypoglycemia, and lactic acidosis.
• Both siblings exhibited severe mtDNA depletion and respiratory chain complex IV deficiency in muscle and liver, without common mtDNA mutations.
• The brother also developed chemical pancreatitis, a previously unreported complication in pediatric mtDNA depletion.

Findings:

• Severe mtDNA depletion can manifest with nonspecific early symptoms like vomiting and failure to thrive.
• Multiorgan involvement, including hepatomegaly, pancreatitis, and myopathy, typically emerges later in the disease course.
• The siblings experienced hepatic failure and hemorrhagic complications, leading to death before six months of age.

Implications:

• Mitochondrial DNA depletion should be included in the differential diagnosis for pediatric cases of failure to thrive or developmental delay of unknown origin.
• Early recognition and diagnosis of mtDNA depletion are crucial for potential management and genetic counseling.
• This case highlights the potential for severe, early-onset presentation and novel complications like pancreatitis in mtDNA depletion disorders.