Skeletal muscle pathology in MNGIE patients: blood vessels depletion

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by ptosis and progressive external ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility, cachexia, leukoencephalopathy and mitochondrial DNA depletion, multiple deletions, or both. This disorder is caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP) a cytosolic enzyme that catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1-phosphate. In MNGIE patients. TP activity is very low or absent resulting in dramatically elevated levels of plasma thymidine and deoxyuridine. TP is expressed in most human tissues but is not expressed in skeletal muscle usually affected in MNGIE suggesting that TP deficiency causes the disease through a toxic intermediate. In addition, TP is associated with angiogenesis and high concentrations of thymidine inhibit microvessels formation. In our preliminary study vessels number between two MINGIE patients and eleven controls was compared. Histologic slides were stained with Alkaline Phosphatase and ratio between blood vessels and fibres number was calculated for each sample. Even if cases and controls numbers are low and they have to be increased, a significative differerence between MINGIE and control patients was revealed suggesting that angiogenesis inhibition could be involved in MINGIE pathogenesis.