TY  - JOUR
A1  - Rickert, V.
A1  - Wagenhäuser, L.
A1  - Nordbeck, P.
A1  - Wanner, C.
A1  - Sommer, C.
A1  - Rost, S.
A1  - Üçeyler, N.
T1  - Stratification of Fabry mutations in clinical practice: a closer look at α‐galactosidase A‐3D structure
JF  - Journal of Internal Medicine
N2  - Background
Fabry disease (FD) is an X‐linked lysosomal storage and multi‐system disorder due to mutations in the α‐galactosidase A (α‐GalA) gene. We investigated the impact of individual amino acid exchanges in the α‐GalA 3D‐structure on the clinical phenotype of FD patients.

Patients and methods
We enrolled 80 adult FD patients with α‐GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α‐GalA 3D‐structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD‐specific treatment.

Results
Patients with active site or buried mutations showed a severe phenotype with multi‐organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α‐GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso‐Gb3 levels were higher (P < 0.01 in men; <0.05 in women).

Conclusions
The type of amino acid exchange location in the α‐GalA 3D‐structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients.
KW  - Fabry disease
KW  - Fabry genotype
KW  - Fabry phenotype
KW  - lyso‐Gb3
KW  - α‐GalA 3D‐structure
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218125
VL  - 288
IS  - 5
SP  - 593
EP  - 604
ER  -