Intractable secretory diarrhea in a Japanese boy with mitochondrial respiratory chain complex I deficiency

Eur J Pediatr. 2009 Mar;168(3):297-302. doi: 10.1007/s00431-008-0753-7. Epub 2008 Jun 17.


The etiology of secretory diarrhea in early life is often unclear. We report a Japanese boy who survived until 3 years of age, despite intractable diarrhea commencing soon after birth. The fecal sodium content was strikingly high (109 mmol/L [normal range, 27-35 mmol/L]) and the osmotic gap was decreased (15 mOsm/kg), consistent with the findings of congenital sodium diarrhea. We examined the mitochondrial respiratory chain function by blue native polyacrylamide gel electrophoresis (BN-PAGE) in-gel enzyme staining, BN-PAGE western blotting, respiratory chain enzyme activity assay, and immunohistochemistry. Liver respiratory chain complex (Co) I activity was undetectable, while other respiratory chain complex activities were increased (Co II, 138%; Co III, 153%; Co IV, 126% versus respective control activities). Liver BN-PAGE in-gel enzyme staining and western blotting showed an extremely weak complex I band, while immunohistochemistry showed extremely weak staining for the 30-kDa subunit of complex I, but normal staining for the 70-kDa subunit of complex II. The patient was, therefore, diagnosed with complex I deficiency. The overall complex I activity of the jejunum was substantially decreased (63% of the control activity). The immunohistochemistry displayed apparently decreased staining of the 30-kDa complex I subunit, together with a slightly enhanced staining of the 70-kDa complex II subunit in intestinal epithelial cells. These data imply that intestinal epithelial cells are also complex I-deficient in this patient. Complex I deficiency is a novel cause of secretory diarrhea and may act via disrupting the supply of adenosine triphosphate (ATP) needed for the maintenance of ion gradients across membranes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / complications
  • Acidosis, Lactic / diagnosis
  • Blood Gas Analysis
  • Child, Preschool
  • Diarrhea, Infantile / diagnosis*
  • Diarrhea, Infantile / enzymology*
  • Diarrhea, Infantile / etiology
  • Electron Transport Complex I / analysis
  • Electron Transport Complex I / deficiency*
  • Fatal Outcome
  • Feces / chemistry
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / pathology
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mitochondrial Diseases / complications*
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / enzymology*
  • Sodium / analysis
  • Sodium / blood
  • Sodium / urine
  • Water-Electrolyte Balance


  • Sodium
  • Electron Transport Complex I