Abstract Mitochondrial DNA (mtDNA) depletion syndrome is a rare cause of hepatic dysfunction in the pediatric population. It is caused by mutations in either mitochondrial or nuclear DNA (nDNA) that result in a quantitative reduction in mtDNA and, in turn, dysfunctional oxidative phosphorylation. In infants, it results in the hepatocerebral phenotype characterized by hyperbilirubinemia, coagulopathy, lactic acidosis, hypoglycemia, lethargy, encephalopathy, developmental delay, and hypotonia. Three infants diagnosed with mtDNA depletion syndrome at The Children's Hospital of Philadelphia were identified and their clinical presentation, disease course, and histologic and ultrastructural features of liver samples (premortem and postmortem) were characterized. While a different mutant gene was identified in each child, they all showed clinical evidence of metabolic dysfunction soon after birth and expired by 1 year of age. Steatosis, cholestasis, and cytoplasmic crowding by atypical mitochondria were consistent pathologic liver findings. Other findings included hepatocyte hypereosinophilia, fibrosis, and hemosiderosis. The infantile form of mtDNA depletion syndrome is exceedingly rare with few published case reports. This study presents a series of 3 patients with mtDNA depletion syndrome diagnosed at a single institution. Although the number of affected patients is small, it represents one of the largest reported series and is the first to establish the important clinical and pathologic features of mtDNA depletion syndrome in infants and young children. Recognizing these characteristics will facilitate early recognition and appropriate treatment of this rare disorder. Key Words: DNA depletion, liver, metabolic dysfunction, mitochondria, pediatric.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The purpose of this statement is to review the literature regarding mitochondrial disease and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are engaged in diagnosing and treating these patients.
The Writing Group members were appointed by the Mitochondrial Medicine Society. The panel included members with expertise in several different areas. The panel members utilized a comprehensive review of the literature, surveys, and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve.
Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease.
The Delphi process enabled the formation of consensus-based recommendations. We hope that these recommendations will help standardize the evaluation, diagnosis, and care of patients with suspected or demonstrated mitochondrial disease.Genet Med 17 9, 689-701.
Genetics in medicine: official journal of the American College of Medical Genetics 12/2014; 17(9). DOI:10.1038/gim.2014.177 · 7.33 Impact Factor
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