title: Mitochondrial neurogastrointestinal encephalopathy in an Indian family with possible manifesting carriers of heterozygous TYMP mutation.
abstract: BACKGROUND
  Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a distinctive autosomal recessive disorder with mitochondrial alterations due to mutations TYMP gene encoding thymidine phosphorylase.
  
  
  METHODS
  Study of clinical and biochemical characteristics of a family with MNGIE.
  
  
  RESULTS
  Index case was a 32 year old man presenting with recurrent vomiting, early satiety and progressive weight loss. He had ptosis, restricted eye movements, generalized muscle wasting, and absent tendon reflexes. Lactate levels were elevated in venous blood and CSF lactate. MRI brain showed diffuse leucoencephalopathy. Barium swallow showed near total obstruction at mid portion of vertical limb of duodenum with ileus. Esophageal manometry suggested myopathy. Muscle biopsy revealed moderate numbers of ragged blue and ragged red fibers as well as cytochrome c oxidase deficient fibers. An elder brother had similar symptoms and expired after a surgical procedure and a 28 year old brother has similar illness. The father had asymptomatic bilateral ptosis with mild ophthalmoparesis. The paternal grandfather and paternal aunt also had bilateral ptosis. Clinical diagnosis of MNGIE was confirmed in the two living brothers by demonstrating severe defects of thymidine phosphorylase activity in buffy coat, elevated thymidine and deoxyuridine in plasma, and a homozygous TYMP c.893G>A mutation.
  
  
  CONCLUSIONS
  This family with biochemically and genetically confirmed mitochondrial neurogastrointestinal encephalopathy syndrome uncharacteristically included heterozygous TYMP mutation carriers manifesting extra-ocular weakness. It is important to identify MNGIE patients early because therapeutic options are emerging.
authors.affiliation: Department of Neurology, National Institute of Mental health and Neurosciences, Bangalore, India. atchayaramnalini@yahoo.co.in
authors.forename: Atchayaram
authors.initials: A
authors.lastname: Nalini
authors.forename: Narayanappa
authors.initials: N
authors.lastname: Gayathri
mesh_terms: D000328:Adult; D006580:Genetic Carrier Screening; D006801:Humans; D007194:India / Q000208:ethnology; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D039141:Muscular Dystrophy, Oculopharyngeal; D009154:Mutation / Q000235:genetics*; D009886:Ophthalmoplegia / Q000151:congenital; D010375:Pedigree; D013939:Thymidine Phosphorylase / Q000235:genetics*; D028361:Mitochondrial Diseases
chemical_list: C543750:TYMP protein, human; D013939:Thymidine Phosphorylase