Strong increase of leukocyte apha-galactosidase A activity in two male patients with Fabry disease following oral chaperone therapy.

ABSTRACT: BACKGROUND:Fabry disease (OMIM 301500) is an X-linked disorder caused by alpha-galactosidase A (?-Gal A) deficiency. The administration of a pharmacologic chaperone (migalastat) in Fabry patients with amenable mutations has been reported to improve or stabilize organ damages and reduce lyso-Gb3 plasma level. An increase of ?-Gal A activity has been observed in vitro in cells expressing amenable GLA mutations when incubated with migalastat. The impact of the drug on ?-Gal A in vivo activity has been poorly studied. METHODS:We conducted a retrospective analysis of two unrelated male Fabry patients with p.Asn215Ser (p.N215S) variant. RESULTS:We report the important increase of ?-Gal A activity in blood leukocytes reaching normal ranges of activity after about 1 year of treatment with migalastat. Cardiac parameters improved or stabilized with the treatment. CONCLUSION:We confirm in vivo the effects of migalastat that have been observed in N215S carriers in vitro. The increase of ?-Gal A activity may be the strongest marker for biochemical efficacy. The normalization of enzyme activity could become the new therapeutic target to achieve.

SUBMITTER: Lamari F 

PROVIDER: S-EPMC6732277 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature