Universität zu Köln

Lenders, Malte, Weidemann, Frank, Kurschat, Christine, Canaan-Kuehl, Sima, Duning, Thomas, Stypmann, Joerg, Schmitz, Boris ORCID: 0000-0001-7041-7424, Reiermann, Stefanie, Kraemer, Johannes, Blaschke, Daniela, Wanner, Christoph, Brand, Stefan-Martin and Brand, Eva (2016). Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant. Orphanet J. Rare Dis., 11. LONDON: BMC. ISSN 1750-1172

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Abstract

Background: Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma. Methods: To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/c.427G>A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations. Results: p.A143T patients suffering from stroke/transient ischemic attacks had slightly decreased residual GLA activities, and/or increased lyso-Gb3 levels, suspecting FD. However, most male p.A143T patients presented with significant residual GLA activity (similar to 50 % of reference), which was associated with normal lyso-Gb3 levels. Additionally, p.A143T patients showed less severe FD-typical symptoms and absent FD-typical renal and cardiac involvement in comparison to FD patients with other missense mutations. Two tested female p.A143T patients with stroke/TIA did not show skewed X chromosome inactivation. No accumulation of neurologic events in family members of p.A143T patients with stroke/transient ischemic attacks was observed. Conclusions: We conclude that GLA p.A143T seems to be most likely a neutral variant or a possible modifier instead of a disease-causing mutation. Therefore, we suggest that p.A143T patients with stroke/transient ischemic attacks of unknown etiology should be further evaluated, since the diagnosis of FD is not probable and subsequent ERT or chaperone treatment should not be an unreflected option.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lenders, Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Weidemann, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurschat, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Canaan-Kuehl, Sima UNSPECIFIED UNSPECIFIED UNSPECIFIED Duning, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Stypmann, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Boris UNSPECIFIED orcid.org/0000-0001-7041-7424 UNSPECIFIED Reiermann, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraemer, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Wanner, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Brand, Stefan-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Brand, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-275987
DOI:	10.1186/s13023-016-0441-z
Journal or Publication Title:	Orphanet J. Rare Dis.
Volume:	11
Date:	2016
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1750-1172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENZYME REPLACEMENT THERAPY; GENE-MUTATIONS; YOUNG-PATIENTS; STROKE; PREVALENCE; PLASMA Multiple languages Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27598