Mitochondrial Diabetes Mellitus with Mitochondrial DNA 3316G>A Mutation: A Unique Autopsy Case Presenting with Sepsis-Associated Cholestasis

Abstract Background: We describe a unique autopsy case of mitochondrial diabetes mellitus (MDM) with mitochondrial DNA 3316G>A mutation, in which, a characteristic sepsis-associated cholestasis was finally recognized via the pathological examinations, and the clinical diagnosis of the cause of jaundice with conjugated hyperbilirubinemiawas very difficult. Case Presentation: A 74-year-old Japanese female was diagnosed with MDM showing a point mutation at mitochondrial DNA 3316G>A on the age of 38. She had been treated with hemodialysis due to the diabetic nephropathy and end-stage renal failure since the age of 66. She noticed urinary tract infection and diabetic gangrene of foot with Gram-negative Bacteroides fragilis bacteremia, followed by aggressive jaundice with high serum level of direct bilirubin, and died 2 months after the symptom onset. At autopsy, multiple foci of bacteremia-induced hemorrhagic infarction were observed in the congestive bilateral lungs, whereas the cholestatic liver revealed no overt gross cholangiectasis. Microscopic findings characteristically showed many bile thrombi in the biliary canaliculi of hepatic lobules without any evidence of severe shock liver. Finally, we diagnosed exclusively and conclusively as sepsis-associated cholestasis due to the marked elevation of Gram-negative bacteria-derived endotoxins and inflammatory cytokines. Conclusion: We propose that these unique liver features in our MDM case might be one of new clues to unveil its enigmatic etiology. Further prospective studies are needed to validate the presence and significance of sepsis-associated cholestasis, after collecting and investigating a larger number of MDM cases with mitochondrial DNA 3316 mutation examined.