Gastroenterology
Volume 137, Issue 1 , Pages 101-109, July 2009

Frequency of Mitochondrial Defects in Patients With Chronic Intestinal Pseudo-Obstruction

  • Aurélien Amiot

      Affiliations

    • AP-HP, Hôpital Beaujon, Pôle des maladies de l'appareil digestif, Service de Gastroentérologie et d'assistance nutritive, Clichy, France
    • Université Paris Diderot-Paris, Paris, France
    • INSERM, U975, Hôpital de La Salpêtrière, Paris, France
  • ,
  • Maya Tchikviladzé

      Affiliations

    • AP-HP, Hôpital de La Salpêtrière, Centre de référence des maladies neuromusculaires, Paris, France
  • ,
  • Francisca Joly

      Affiliations

    • AP-HP, Hôpital Beaujon, Pôle des maladies de l'appareil digestif, Service de Gastroentérologie et d'assistance nutritive, Clichy, France
    • Université Paris Diderot-Paris, Paris, France
  • ,
  • Abdelhamid Slama

      Affiliations

    • AP-HP, Hôpital Bicêtre, Service de Biochimie, Le Kremlin-Bicêtre, France
  • ,
  • Dominique Cazals Hatem

      Affiliations

    • Université Paris Diderot-Paris, Paris, France
    • AP-HP, Hôpital Beaujon, Service d'anatomie pathologique, Clichy, France
  • ,
  • Claude Jardel

      Affiliations

    • INSERM, U975, Hôpital de La Salpêtrière, Paris, France
    • AP-HP, Hôpital de La Salpêtrière, Service de Biochimie Métabolique, Paris, France
  • ,
  • Bernard Messing

      Affiliations

    • AP-HP, Hôpital Beaujon, Pôle des maladies de l'appareil digestif, Service de Gastroentérologie et d'assistance nutritive, Clichy, France
    • Université Paris Diderot-Paris, Paris, France
  • ,
  • Anne Lombès

      Affiliations

    • INSERM, U975, Hôpital de La Salpêtrière, Paris, France
    • AP-HP, Hôpital de La Salpêtrière, Service de Biochimie Métabolique, Paris, France
    • Université Pierre et Marie Curie-Paris 6 UPMC-Paris 6, Paris, France
    • Corresponding Author InformationReprint requests Address requests for reprints to: Anne Lombès, MD, PhD, INSERM 975, Hôpital Pitié-Salpêtrière,75651 Paris Cedex 13, France; fax: +331 40 16 57 00

Received 17 December 2008; accepted 23 March 2009. published online 03 April 2009.

Background & Aims

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder caused by intestinal dysmotility and characterized by chronic symptoms suggesting bowel obstruction in the absence of fixed, occluding lesions. CIPO has been associated with primary defects of the mitochondrial oxidative phosphorylation pathway, although the frequency of mitochondrial disorders in patients with CIPO is unknown. This study evaluates mitochondrial function in patients with CIPO.

Methods

A retrospective study was performed of data collected from 80 CIPO patients at a tertiary centre over a 25-year period. Mitochondrial disorders were detected by analysis of serum lactate and thymidine phosphorylase activities, brain magnetic resonance images, and muscle biopsies. Genes encoding thymidine phosphorylase, mitochondrial DNA tRNAleu(UUR) or tRNAlys, and DNA polymerase-γ were analyzed for mutations.

Results

Mitochondrial defects were identified in 15 patients (10 women; median age at diagnosis 32 years), representing 19% of the study cohort. All 15 patients had extra-digestive symptoms, 5 had mutations in the thymidine phosphorylase gene, 2 had mutations in tRNAleu(UUR), and 5 had mutations in the DNA polymerase-γ gene. No genetic defect was detected in 3 of the patients with mitochondrial disorders. Patients with mitochondrial CIPO differed from patients without mitochondrial defects in their very severe nutritional status (frequent and long-term requirement for parenteral nutrition) and poor prognosis (frequent digestive and neurologic complications that led to a high incidence of premature death).

Conclusion

Mitochondrial disorders seem to be an important cause of CIPO. Patients with CIPO, especially severe cases with associated neurologic symptoms, should be tested for mitochondrial defects.

Abbreviations used in this paper: BMI, body mass index, CIPO, chronic intestinal pseudo-obstruction, MELAS, mitochondrial myopathy, epilepsy, lactic acidosis and strokelike episodes, MNGIE, mitochondrial neurogastrointestinal encephalomyopathy, MtDNA, mitochondrial DNA, POLG, polymerase gamma gene, SDH, succinate dehydrogenase

 

 To view this article's video abstract, go to the AGA's YouTube Channel.

 Conflicts of interest The authors disclose no conflicts.

 Funding Aurélien Amiot was the recipient of a fellowship from Sanofi-Aventis. The work was supported by grant from the Association Française contre les myopathies (AFM).

PII: S0016-5085(09)00518-6

doi:10.1053/j.gastro.2009.03.054

Gastroenterology
Volume 137, Issue 1 , Pages 101-109, July 2009