Background Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive condition, characterised by peripheral neuropathy, gastrointestinal dysmotility, asymptomatic cerebral white matter lesions and mitochondrial myopathy, and caused by mutations in the gene for thymidine phosphorylase (TP).

Methods The standard method of diagnosing MNGIE comprises detection of raised plasma concentrations of substrates for TP, thymidine and deoxyuridine, and low or absent TP activity in buffy coat, platelets or leucocytes. In the course of molecular genetic studies on two patients with MNGIE, diagnosed by the standard method, we used a monoclonal antibody against TP to show on Western blots that TP protein was undetectable in the patients' fibroblasts. We have now extended this technique to immunoblots of platelet protein extracts.

Results TP was readily detectable in control platelets but absent from the patients'. This was the case even for a patient in whom one TP mutation consisted solely of a deletion of two amino acid residues.

Conclusion These findings suggest a possible use of anti-TP monoclonal antibodies in screening for a diagnosis of MNGIE. Our immunoblot approach may also help to discriminate molecular mechanisms in the pathogenesis of MNGIE, i.e., whether the enzyme deficiency is caused by diminished activity or protein instability.