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

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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.

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Abbreviations

BN-PAGE:

Blue native polyacrylamide gel electrophoresis

Co:

Complex

CS:

Citrate synthase

CMVA:

Congenital microvillous atrophy

ATP:

Adenosine triphosphate

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Acknowledgments

We would like to thank Hiroko Harashima for technical assistance and Robert Taylor for the mtDNA sequence analysis. This work was supported in part by a grant-in-aid for scientific research (no. 16591052) from the Japan Society for the Promotion of Science (JSPS) and by the National Health and Medical Research Council (NHMRC, Australia). DRT is supported by an NHMRC Principal Research Fellowship.

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Correspondence to Kei Murayama.

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Murayama, K., Nagasaka, H., Tsuruoka, T. et al. Intractable secretory diarrhea in a Japanese boy with mitochondrial respiratory chain complex I deficiency. Eur J Pediatr 168, 297–302 (2009). https://doi.org/10.1007/s00431-008-0753-7

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  • DOI: https://doi.org/10.1007/s00431-008-0753-7

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