Variant transthyretin (TTR) amyloidosis in Argentina. Detection of the trait by electrospray ionization mass spectrometry of lyophilized TTR immunoprecipitate

We have developed a quick and reliable diagnostic method for detecting vari ant forms of transthyretin (TTR); namely, centrifugal concentration followe d by electrospray ionization mass spectrometry (ESI-MS). Argentinian patien ts from three families with neuropathic amyloidosis and their relatives wer e screened for mutated TTR by ESI-MS. In order to facilitate transportation , we investigated the impact storage had on lyophilized anti-TTR-antibody p recipitates' mass spectra. For this investigation, plasma samples from thre e Swedish patients with known TTR amyloidosis were analysed. We detected id entical, additional peaks corresponding to a variant form of TTR in 10 memb ers of the families, and also in a lyophilized sample sent unfrozen by mail from Argentina. All except one symptomatic subject had additional peaks, t he exception having undergone a liver transplantation for the disease. All patients were early onset cases, i.e. below 35 years of age, and family his tory suggests an aggressive, rapidly progressing disease. Lyophilized anti- TTR-antibody precipitates stored at room temperature for 1 week exhibited o nly minor differences compared with plasma samples stored at -70 degrees C. In a new Argentinian study on familial amyloidotic polyneuropathy, the var iant TTR was quickly identified and typed by ESI-MS. To facilitate transpor tation, dry-frozen samples can be used and the quality of the spectra is si milar to that of samples stored at -70 degrees C.