title: [Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE): When and how to suspect it in front of an atypical anorexia nervosa?]
abstract: BACKGROUND
  The Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) disease is an extremely underrated syndrome beginning around the age of eighteen years. Because of its severity, this diagnosis should be considered when a patient presents an atypical anorexia nervosa. MNGIE disease is inherited in an autosomal recessive manner and related to mutations of the TYMP gene (ch22q13.32-qter), encoding the thymidine phosphorylase. The MNGIE is often misdiagnosed and is associated with a time to diagnostic of about 12 years after first symptoms. Thus this critical review aims to help clinicians better identify symptoms and paraclinical markers of the MNGIE as a differential diagnosis of atypical anorexia nervosa.
  
  
  METHODS
  A literature search was performed using PubMed and Google Scholar databases.
  
  
  RESULTS
  The clinical diagnosis of the MNGIE disease should be based on the association of severe loss of weight and some additional symptoms: (1) severe gastrointestinal dysmotility (nausea, vomiting, intestinal pseudo-obstruction), (2) ptosis or external ophtalmoplegia and (3) peripheral sensorimotor neuropathy. When MNGIE disease is clinically suspected, paraclinical testing can help to validate the MNGIE diagnostic: (1) Arterial blood test reveals lactic acidemia (e.g. an increased serum concentration of lactate without pH modifications), and (2) Brain MRI indicates leukoencephalopathy, usually asymptomatic. Direct evidence of MNGIE disease is based on specific testing of: (1) the thymidine phopshorylase enzyme activity in leukocytes is less than 10% of the control, (2) the increase of plasmatic thymidine (>3μmol/L) and the increase of plamatic deoxyuridine (>5μmol/L), (3) the evidence of mutations of the TYMP gene by molecular genetic testing.
  
  
  CONCLUSIONS
  The MNGIE disease is a severe trouble with multisystemic complications. The thymidine phopshorylase enzyme activity in leukocytes should be measured as soon as possible when a patient presents atypical anorexia nervosa.
authors.affiliation: Clinique Aloise-Corbaz, centre hospitalier d'Arras, boulevard Georges-Besnier, 62000 Arras, France. Electronic address: mdanjou@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Danjou
authors.affiliation: Clinique Lautréamont, 59120 Loos, France.
authors.forename: D
authors.initials: D
authors.lastname: Guardia
authors.affiliation: Inserm, U1144, 75006 Paris, France; Pôle neurosciences, groupe hospitalier Saint-Louis-Lariboisière-Fernand-Widal, AP-HP, 75475 Paris cedex 10, France; Université Lille-Nord-de-France, 59000 Lille, France.
authors.forename: P-A
authors.initials: PA
authors.lastname: Geoffroy
authors.affiliation: Université Lille-Nord-de-France, 59000 Lille, France; Unité mobile de soutien nutritionnel, centre hospitalier universitaire de Lille (CHRU), 59037 Lille, France; Inserm, U995, université Lille-Nord-de-France, 59000 Lille, France.
authors.forename: D
authors.initials: D
authors.lastname: Seguy
authors.affiliation: Université Lille-Nord-de-France, 59000 Lille, France; Psychiatry department, centre hospitalier universitaire de Lille (CHRU), 59037 Lille, France.
authors.forename: O
authors.initials: O
authors.lastname: Cottencin
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000856:Anorexia Nervosa / Q000175:diagnosis* / Q000523:psychology* / Q000628:therapy; D002648:Child; D006801:Humans; D007418:Intestinal Pseudo-Obstruction; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology* / Q000628:therapy; D035583:Rare Diseases; D013939:Thymidine Phosphorylase / Q000235:genetics
chemical_list: C543750:TYMP protein, human; D013939:Thymidine Phosphorylase
keywords: Anorexia; Anorexie; Diagnostic différentiel; Differential diagnosis; Genetic disease; MNGIE; Maladie génétique; Maladie orpheline; Orphan disease