TY  - JOUR
A1  - Oder, Daniel
A1  - Üceyler, Nurcan
A1  - Liu, Dan
A1  - Hu, Kai
A1  - Petritsch, Bernhard
A1  - Sommer, Claudia
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
T1  - Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y
JF  - BMJ Open
N2  - Objectives: The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function.

Setting and participants: In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included.

Primary and secondary outcome measures: Cardiac, nephrological, neurological, laboratory and quality of life data.

Results: AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain −21.6±1.9%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter.

Conclusions: The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD."
KW  - inherited metabolic disorders
KW  - Anderson-Fabry Disease
KW  - D313Y genotype
KW  - Fabry cardiomyopathy
KW  - Fabry nephropathy
KW  - Fabry-associated pain
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161210
VL  - 6
ER  -