Mitochondrial DNA depletion in children
C Y Tsao1, J R Mendell, M Luquette
1Department of Pediatrics and Neurology, College of Medicine and Public Health, The Ohio State University, Columbus 43205, USA. ctsao@chi.osu.edu
Insights
Severe mitochondrial DNA depletion caused failure to thrive, organ damage, and early death in two infants. This condition requires consideration in diagnosing children with unexplained developmental delays.
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.
Abstract:
The first girl of an unrelated couple was noted to have failure to thrive since age 3 months, generalized hypotonia and weakness, hepatomegaly, hypoglycemia, and lactic acidosis at 4 months. She was found to have severe mitochondrial DNA (mtDNA) depletion and respiratory chain complex IV deficiency in both skeletal muscle and liver but without other common mtDNA mutations. Her younger brother developed vomiting at age 3 weeks and was diagnosed as having pyloric stenosis. His skeletal muscle and liver also showed severe mtDNA depletion. He developed generalized weakness and hypotonia, hepatomegaly, and lactic acidosis at age 3 months. Both siblings died of hepatic failure and hemorrhagic complication before 6 months of age. The brother also had chemical pancreatitis, which had not been reported before in mtDNA depletion in children. Severe mtDNA depletion may present with nonspecific symptoms such as vomiting, failure to thrive, and developmental delay; multiorgan involvement such as hepatomegaly, pancreatitis, and myopathy occurs later. Mitochondrial DNA depletion should be considered in the differential diagnosis in children with developmental delay or failure to thrive of unknown etiology.
Related Concept Videos
02:59Animal Mitochondrial Genetics
01:37Mitochondria
01:45Mitochondrial Membranes