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Objective: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with α-galactosidase A (α-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population., Methods: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed., Results: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot α-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation., Conclusions: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The risk of pulmonary vein narrowing (PVN) after pulmonary vein isolation, using a novel multi-electrode ablation catheter, is unknown., Methods and Results: Left atrial volume and PV diameters were compared by computed tomography (CT) before and 3 months after pulmonary vein isolation using duty-cycled phased radio frequency energy (2:1 or 4:1 bipolar/unipolar ratio) in 50 patients. Pulmonary vein diameter was measured in a coronal and axial view at 3 levels (A, ostium; B, 1 cm more distal; C, 2 cm more distal). Moderate PVN was defined as a pulmonary vein diameter reduction of 25 to 50%, and severe PVN as >50%. Left atrial volume decreased by 12±12% (P<0.01). Axial pulmonary vein diameter shortened by a median of 16% (interquartile range [IQR] 28 to 5%), 13% (IQR 25 to 5%), and 9% (IQR 21 to -3%) at level A, B, and C, respectively (P<0.01 for all); coronal pulmonary vein diameter decreased by a median of 16% (IQR 24 to 7%), 11% (IQR 21 to 4%), and 8% (IQR 18 to -2%; P<0.01 for all). Moderate PVN occurred in 30% of the PVs, in 78% of the patients; severe PVN occurred in 4% of the PVs, in 15% of the patients. PV diameter reduction was not related to changes in left atrial volume., Conclusions: Isolation of the pulmonary veins using a multielectrode ablation catheter and duty cycled phased radiofrequency energy delivery results in a consistent moderate reduction of the PV diameters predominantly at the ostium. Severe PVN in 15% of patients raises concerns about the risk for clinical PV stenosis.