TY  - JOUR
A1  - Lenders, Malte
A1  - Hennermann, Julia B.
A1  - Kurschat, Christine
A1  - Rolfs, Arndt
A1  - Canaan-Kühl, Sima
A1  - Sommer, Claudia
A1  - Üçeyler, Nurcan
A1  - Kampmann, Christoph
A1  - Karabul, Nesrin
A1  - Giese, Anne-Katrin
A1  - Duning, Thomas
A1  - Stypmann, Jörg
A1  - Krämer, Johannes
A1  - Weidemann, Frank
A1  - Brand, Stefan-Martin
A1  - Wanner, Christoph
A1  - Brand, Eva
T1  - Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease
JF  - Orphanet Journal of Rare Diseases
N2  - Background
The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines.

Methods
Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.

Results
Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-naïve females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-naïve females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso-Gb3 levels.

Conclusion
The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females.
KW  - Fabry disease
KW  - females
KW  - lyso-Gb3
KW  - enzyme replacement therapy
KW  - guidelines
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166543
VL  - 11
IS  - 88
ER  - 
TY  - JOUR
A1  - Lenders, Malte
A1  - Weidemann, Frank
A1  - Kurschat, Christine
A1  - Canaan-Kühl, Sima
A1  - Duning, Thomas
A1  - Stypmann, Jörg
A1  - Schmitz, Boris
A1  - Reiermann, Stefanie
A1  - Krämer, Johannes
A1  - Blaschke, Daniela
A1  - Wanner, Christoph
A1  - Brand, Stefan-Martin
A1  - Brand, Eva
T1  - Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant
JF  - Orphanet Journal of Rare Diseases
N2  - 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 (~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.
KW  - Fabry disease
KW  - genotype
KW  - lyso-Gb3
KW  - variant of unknown significance
KW  - GLA mutation
KW  - late-onset
KW  - stroke
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166559
VL  - 11
IS  - 54
ER  -