title: Mutant α-galactosidase A with M296I does not cause elevation of the plasma globotriaosylsphingosine level.
abstract: Recently, 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.
authors: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors: Sayuri
authors: S
authors: Mitobe
authors: Tadayasu
authors: T
authors: Togawa
authors: Takahiro
authors: T
authors: Tsukimura
authors: Takashi
authors: T
authors: Kodama
authors: Toshie
authors: T
authors: Tanaka
authors: Kent
authors: K
authors: Doi
authors: Eisei
authors: E
authors: Noiri
authors: Yasuhiro
authors: Y
authors: Akai
authors: Yoshihiko
authors: Y
authors: Saito
authors: Makoto
authors: M
authors: Yoshino
authors: Toshihiro
authors: T
authors: Takenaka
authors: Seiji
authors: S
authors: Saito
authors: Kazuki
authors: K
authors: Ohno
authors: Hitoshi
authors: H
authors: Sakuraba
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000235:genetics; D008297:Male; D008715:Methionine / Q000737:chemistry / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013107:Sphingolipids / Q000097:blood*; D000519:alpha-Galactosidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; D007532:Isoleucine; C063288:globotriaosyl lysosphingolipid; D008715:Methionine; D000519:alpha-Galactosidase