Using the unique preparation and detection techniques we devised for application of proteins to soft ionization mass spectrometry, we found many variant and abnormally modified proteins. Up to end of 2002, we have diagnosed 96 cases of variant hemoglobins(Hb), which include 45 different and 3 new species. We have diagnosed or confirmed the molecular weight difference of 64 cases of variant transthyretins (TTR), which include 14 different and 3 new species. We found the first 2 cases showing homozygote of TTR 119Thr→Met, a high frequent non-amyloid variant among some European ethnicities. Variants of Cu, Zn-superoxide dismutase, 5 cases, 5 different species, were analyzed and the differences of molecular weight suggested by DNA analyses were confirmed. These are listed in the text.
Cysteine 10 in TTR is modified in vivo and in vitro. We found a marked increase in s-sulfonated TTR in 4 patients with molybdenum cofactor deficiency and homocysteine conjugated TTR in 2 patients with methylene H4 folate reductase deficiency. The carbohydrate deficient transferrin was detected in 3 cases of carbohydrate deficient glycoprotein syndrome. The detection of these modified structures might be expected to be a new diagnostic index for these diseases, which are easily misdiagnosed.
The improved reference method for HbA1C measurement was established using isotope(deuterium) labeled glycated and non-glycated hexapeptides from amino terminal of Hb β-chain. We checked the discrepancies of HbA1C values by the routine method and the reference method we established. Most samples containing variant Hbs did not show correct HbA1C values by HPLC and some did not show correct values by immunoassay. We showed a typical example of an enormous increase in the glycation degree because of the amino acid substitution, which was shown clearly by electrospray ionization/mass spectrometry. (Nine figures and 4 tables were selected from 45 slides presented in the lecture.)

*Department of Clinical Pathology, Osaka Medical College, Takatsuki 569-8686