Refine
Has Fulltext
- yes (6)
Is part of the Bibliography
- yes (6)
Document Type
- Journal article (6)
Language
- English (6)
Keywords
- Fabry disease (3)
- enzyme replacement therapy (2)
- lyso-Gb3 (2)
- 2-dimensional speckle tracking (1)
- Chronic kidney disease (1)
- Fabry nephropathy (1)
- Fabry patient (1)
- GLA mutation (1)
- LV mass (1)
- Quality of life (1)
- SF-36 (1)
- biomarker (1)
- cardiac hypertrophy (1)
- cardiomyopathy (1)
- cardiovascular magnetic resonance (1)
- clinical manifestations (1)
- cornea verticillata (1)
- diabetic mouse (1)
- diagnosis (1)
- disease (1)
- fabry disease (1)
- females (1)
- fibrosis (1)
- genotype (1)
- guidelines (1)
- hypertrophic cardiomyopathy (1)
- identification (1)
- impact (1)
- late-onset (1)
- left ventricular mass (1)
- myocardial infarction (1)
- myocardial fibrosis (1)
- renal fibrosis (1)
- septal hypertrophy (1)
- stroke (1)
- therapy (1)
- troponin T (1)
- urinary protein excretion (1)
- variant of unknown significance (1)
Institute
- Medizinische Klinik und Poliklinik I (4)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Klinische Epidemiologie und Biometrie (1)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (1)
- Medizinische Fakultät (1)
- Neurologische Klinik und Poliklinik (1)
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.