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.
Department of Metabolism, Chiba Children's Hospital, 579-1, Henda-cho, Midori-ku, Chiba, 266-0007, Japan. kmuraya@mri.biglobe.ne.jp
Kei
K
Murayama
Hironori
H
Nagasaka
Tomoko
T
Tsuruoka
Yuko
Y
Omata
Hiroshi
H
Horie
Simone
S
Tregoning
David R
DR
Thorburn
Masaki
M
Takayanagi
Akira
A
Ohtake
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