Get access

Normal oxidative phosphorylation in intestinal smooth muscle of childhood chronic intestinal pseudo-obstruction

Authors

  • L. Galmiche,

    1. Department of Pathology and Tumorothèque, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    2. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • F. Jaubert,

    1. Department of Pathology and Tumorothèque, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • F. Sauvat,

    1. Department of Paediatric Surgery, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • S. Sarnacki,

    1. Department of Paediatric Surgery, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • O. Goulet,

    1. Department of Paediatric Gastroenterology, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • Z. Assouline,

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • V. Vedrenne,

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • A-S. Lebre,

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • N. Boddaert,

    1. Department of Paediatric Radiology, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • N. Brousse,

    1. Department of Pathology and Tumorothèque, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • D. Chrétien,

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • A. Munnich,

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author
  • A. Rötig

    1. INSERM U781 and Department of Genetics, Faculty of Medicine, Hôpital Necker Enfants-Malades and Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France
    Search for more papers by this author

Address for Correspondence
Louise Galmiche, INSERM U781, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France.
Tel: +01 44 38 15 84; fax: +01 47 34 85 14;
e-mail: louise.galmiche@inserm.fr

Abstract

Background Chronic intestinal pseudo-obstruction (CIPO) is a severe disease of the digestive tract motility. In pediatric population, CIPO remains of unknown origin for most patients. Chronic intestinal pseudo-obstruction is also a common feature in the course of mitochondrial oxidative phosphorylation disorders related for some patients to mutations in TYMP, POLG1, mtDNA tRNAleu(UUR) or tRNAlys genes. We hypothesized that CIPOs could be the presenting symptom of respiratory chain enzyme deficiency and thus we investigated oxidative phosphorylation in small bowel and/or colon smooth muscle of primary CIPO children. Methods We studied eight children with CIPO and 12 pediatric controls. We collected clinical, radiological and pathological data and measured respiratory chain enzymatic activity in isolated smooth muscle of the small bowel and/or the colon. We also sequenced TYMP, POLG, mtDNA tRNAleu(UUR) and tRNAlys genes. Key Results Neither pathological nor radiological data were in favor of a mitochondrial dysfunction. No respiratory chain enzyme deficiency was detected in CIPO children. In myogenic CIPO, respiratory enzymes and citrate synthase activities were increased in small bowel and/or colon whereas no abnormality was noted in neurogenic and unclassified CIPO. Levels of enzyme activities were higher in control small bowel than in control colon muscle. Sequencing of TYMP, POLG, mtDNA tRNAleu(UUR) and tRNAlys genes and POLG gene did not reveal mutation for any of the patients. Conclusions & Inferences The normal enzymatic activities as the lack of radiological and genetic abnormalities indicate that, at variance with adult patients, oxidative phosphorylation deficiency is not a common cause of childhood CIPO.

Ancillary