MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation

J Med Genet. 2004 Feb;41(2):125-9. doi: 10.1136/jmg.2003.013789.


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase (TP) deficiency, resulting in severe gastrointestinal dysmotility and skeletal muscle abnormalities. A patient is reported with a classical MNGIE clinical presentation but without skeletal muscle involvement at morphological, enzymatic, or mitochondrial DNA level, though gastrointestinal myopathy was present. MNGIE was diagnosed by markedly raised plasma thymidine and reduced thymidine phosphorylase activity. Molecular genetic analysis showed a homozygous novel splice site mutation in TP. On immunohistochemical studies there was marked TP expression in the CNS, in contrast to what has been observed in rodents. It is important to examine the most significantly affected tissue and to measure TP activity and plasma thymidine in order to arrive at an accurate diagnosis in this condition.

Publication types

  • Case Reports
  • Multicenter Study

MeSH terms

  • Adolescent
  • DNA, Mitochondrial / genetics
  • Fatal Outcome
  • Humans
  • Intestinal Pseudo-Obstruction / diagnosis
  • Intestinal Pseudo-Obstruction / genetics*
  • Male
  • Mitochondrial Encephalomyopathies / diagnosis
  • Mitochondrial Encephalomyopathies / genetics*
  • Muscle, Skeletal / abnormalities*
  • Muscle, Skeletal / pathology
  • Mutation / genetics*
  • RNA Splice Sites / genetics*
  • Thymidine Phosphorylase / genetics*


  • DNA, Mitochondrial
  • RNA Splice Sites
  • Thymidine Phosphorylase