Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination

Ann Neurol. 2016 Nov;80(5):686-692. doi: 10.1002/ana.24736. Epub 2016 Sep 19.

Abstract

Objectives: The m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo-obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A>G-related mitochondrial disease manifesting with IPO.

Methods: In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243A>G-related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion.

Results: Between January 2009 and June 2015, 226 patients harbouring the m.3243A>G mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke-like episodes, whereas 1 presented 27 years previously with their first stroke-like episode. Eight patients developed IPO concomitantly during an acute stroke-like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures.

Interpretation: Our findings suggest, in this common mitochondrial disease, that IPO is an under-recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016;80:686-692.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Intestinal Pseudo-Obstruction / diagnostic imaging*
  • Intestinal Pseudo-Obstruction / etiology
  • Intestinal Pseudo-Obstruction / genetics*
  • Male
  • Middle Aged
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / genetics*
  • Outcome Assessment, Health Care
  • Prevalence
  • RNA, Transfer, Leu / genetics*
  • Stroke / etiology
  • Stroke / genetics*
  • Young Adult

Substances

  • DNA, Mitochondrial
  • RNA, Transfer, Leu