Background. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a disorder with autosomal recessive
inheritance caused by mutations in the gene encoding thymidine phosphorylase (TP). TP deficiency results in
imbalance of mitochondrial pool of nucleotides leading secondary to multiple deletions and depletion of mitochondrial
DNA (mtDNA) and impairment of oxidative phosphorylation system. The disease is clinically characterized by
gastrointestinal dysmotility with symptoms of pseudo-obstruction, severe failure to thrive, ptosis, leukoencephalopathy,
peripheral neuropathy and myopathy. We present results of the clinical, histochemical, biochemical and molecular
analyses of the first Czech patient with MNGIE syndrome.
Methods and Results. Man, 33-years old with twenty-year history of failure to thrive (height 168 cm, weight 34 kg)
and progressive gastrointestinal dysmotility, external ophthalmoplegia, leucoencephalopathy and peripheral neuropathy
was recommended to metabolic center. Histochemical analyses in muscle biopsy showed the presence of „ragged
red fibers“ with focal decrease of cytochrome c oxidase activity, but spectrophotometric analyses in isolated
muscle mitochondria revealed normal activities of all respiratory chain complexes. Metabolic investigation revealed
markedly increased plasma level of thymidine (6.6 μmol/l, controls <0.05 μmol/l) and deoxyuridine (15 μmol/l, controls
<0.05 μmol/l). The activity of TP in isolated lymphocytes was low (0.02 μmol/hour/mg protein, reference range
0.78±0.18). Molecular analyses in muscle biopsy revealed multiple mtDNA deletions and homozygous mutation
1419G>A (Gly145Arg) was found in gene for TP. Both parents are heterozygotes.
Conclusions. MNGIE has to be considered in patients presenting with a combination of gastrointestinal and neurological
symptoms. Plasma level of thymidine may serve as the best method for laboratory screening of MNGIE, but
molecular analyses are necessary for genetic counselling and prenatal diagnosis in affected families.
MNGIE, gastrointestinal dysmotility, thymidine, thymidine phosphorylase, ECGF1.