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J Med Genet 41:125-129 doi:10.1136/jmg.2003.013789
  • Short report

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

  1. K Szigeti1,
  2. L-J C Wong4,
  3. C-L Perng4,
  4. G M Saifi1,
  5. K Eldin2,
  6. A M Adesina2,
  7. D L Cass3,
  8. M Hirano5,
  9. J R Lupski1,
  10. F Scaglia1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA
  2. 2Department of Pathology, Baylor College of Medicine and Texas Children’s Hospital
  3. 3Department of Surgery, Baylor College of Medicine and Texas Children’s Hospital
  4. 4Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington DC, USA
  5. 5Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
  1. Correspondence to:
 Dr James R Lupski
 Baylor College of Medicine, One Baylor Plaza, Rm604B, Houston, Texas 77030, USA; jlupskibcm.tmc.edu
  • Received 26 August 2003
  • Accepted 19 September 2003

Abstract

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.

Footnotes