title: Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Yi Shiau
authors.initials: YS
authors.lastname: Ng
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Feeney
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Schaefer
authors.affiliation: Department of Radiology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Carol Ellen
authors.initials: CE
authors.lastname: Holmes
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Paula
authors.initials: P
authors.lastname: Hynd
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Alston
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Grady
authors.affiliation: The Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Department of Neurology, The Leeds Teaching Hospitals NHS Trust, West Yorkshire, United Kingdom.
authors.forename: Mellisa
authors.initials: M
authors.lastname: Maguire
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bright
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yiannakou
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Gráinne S
authors.initials: GS
authors.lastname: Gorman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000000981:diagnostic imaging* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D015995:Prevalence; D012356:RNA, Transfer, Leu / Q000235:genetics*; D020521:Stroke / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu