Intractable secretory diarrhea in a Japanese boy with mitochondrial respiratory chain complex I deficiency.
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.
Murayama
Kei
K
Department of Metabolism, Chiba Children's Hospital, 579-1, Henda-cho, Midori-ku, Chiba, 266-0007, Japan. kmuraya@mri.biglobe.ne.jp
Nagasaka
Hironori
H
Tsuruoka
Tomoko
T
Omata
Yuko
Y
Horie
Hiroshi
H
Tregoning
Simone
S
Thorburn
David R
DR
Takayanagi
Masaki
M
Ohtake
Akira
A
D000140:Acidosis, Lactic / Q000150:complications / Q000175:diagnosis; D001784:Blood Gas Analysis; D002675:Child, Preschool; D003968:Diarrhea, Infantile / Q000175:diagnosis* / Q000201:enzymology* / Q000209:etiology; D042967:Electron Transport Complex I / Q000032:analysis / Q000172:deficiency*; D017809:Fatal Outcome; D005243:Feces / Q000737:chemistry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications* / Q000175:diagnosis / Q000201:enzymology*; D012964:Sodium / Q000032:analysis / Q000097:blood / Q000652:urine; D014882:Water-Electrolyte Balance
D012964:Sodium; D042967:Electron Transport Complex I