Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y
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- 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 outcomeObjectives: 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."…
Autor(en): | Daniel Oder, Nurcan Üceyler, Dan Liu, Kai Hu, Bernhard Petritsch, Claudia Sommer, Georg Ertl, Christoph Wanner, Peter Nordbeck |
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URN: | urn:nbn:de:bvb:20-opus-161210 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) |
Medizinische Fakultät / Neurologische Klinik und Poliklinik | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik I | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | BMJ Open |
Erscheinungsjahr: | 2016 |
Band / Jahrgang: | 6 |
Seitenangabe: | e010422 |
Originalveröffentlichung / Quelle: | BMJ Open 2016;6:e010422. doi:10.1136/bmjopen-2015- 010422 |
DOI: | https://doi.org/10.1136/bmjopen-2015-010422 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Freie Schlagwort(e): | Anderson-Fabry Disease; D313Y genotype; Fabry cardiomyopathy; Fabry nephropathy; Fabry-associated pain; inherited metabolic disorders |
Datum der Freischaltung: | 12.07.2018 |
Lizenz (Deutsch): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |