Mutant α-galactosidase A with M296I does not cause elevation of the plasma globotriaosylsphingosine level
2012; Elsevier BV; Volume: 107; Issue: 3 Linguagem: Inglês
10.1016/j.ymgme.2012.07.003
ISSN1096-7206
AutoresSayuri Mitobe, Tadayasu Togawa, Takahiro Tsukimura, Takashi Kodama, Toshie Tanaka, Kent Doi, Eisei Noiri, Yasuhiro Akai, Yoshihiko Saito, Makoto Yoshino, Toshihiro Takenaka, Seiji Saito, Kazuki Ohno, Hitoshi Sakuraba,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoRecently, plasma globotriaosylsphingosine (lyso-Gb3) has attracted attention as a biomarker of Fabry disease. However, we found a subset of Fabry disease patients who did not show any increase in the plasma lyso-Gb3 concentration, although other patients exhibited apparent enhancement of it. This subset predominantly exhibited the clinical phenotype of later-onset Fabry disease, and gene analysis revealed that the patients harbored the M296I mutation common to Japanese Fabry patients. This amino acid substitution is predicted to cause a small conformational change on the surface of the α-galactosidase A molecule, resulting in residual enzyme activity. Plasma lyso-Gb3 is a good biomarker of Fabry disease but care should be taken when it is used for a definitive diagnosis.
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