Mitochondrial Neurogastrointestinal Encephalopathy: Clinical, Biochemical and Molecular Study in Three Egyptian Patients

Genet Couns. 2016;27(2):193-205.

Abstract

Background: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy sundrome from two different pedigrees.

Subjects and methods: The three patients were subjected to thorough neurologic examination. Brain Magtnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis.

Results: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of themuscle biopsy revealed deficient cytochrome C oxidase and mitochrondrial respiratory chain enzyme assay revealed isolated complex 1 deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371 A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings.

Conclusions: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagmosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Consanguinity
  • Egypt
  • Female
  • Humans
  • Intestinal Pseudo-Obstruction* / enzymology
  • Intestinal Pseudo-Obstruction* / genetics
  • Intestinal Pseudo-Obstruction* / physiopathology
  • Male
  • Mitochondrial Encephalomyopathies* / enzymology
  • Mitochondrial Encephalomyopathies* / genetics
  • Mitochondrial Encephalomyopathies* / physiopathology
  • Muscular Dystrophy, Oculopharyngeal
  • Ophthalmoplegia / congenital
  • Pedigree
  • Thymidine Phosphorylase / genetics
  • Young Adult

Substances

  • Thymidine Phosphorylase

Supplementary concepts

  • Visceral myopathy familial external ophthalmoplegia