Mutant α-galactosidase A with M296I does not cause elevation of the plasma globotriaosylsphingosine level

► Fabry patients showing no increase in the plasma Lyso-Gb3 level were found. ► This subset exhibited the clinical phenotype of later-onset Fabry disease. ► Gene analysis revealed that the patients harbored the M296I mutation. ► This amino acid substitution is predicted to cause a small conformational change.