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

Abstract

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.

• Authors: Kei Murayama, Hironori Nagasaka, Tomoko Tsuruoka, Yuko Omata, Hiroshi Horie, Simone Tregoning, David R Thorburn, Masaki Takayanagi, Akira Ohtake
• Journal: European journal of pediatrics (Eur J Pediatr) Vol. 168 Issue 3 Pg. 297-302 (Mar 2009) ISSN: 1432-1076 [Electronic] Germany
• PMID: 18560889 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium
• Electron Transport Complex I

Topics

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