Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease

Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 67-73 ◽  
Author(s):  
Olga Azevedo ◽  
Miguel Gago ◽  
Gabriel Miltenberger-Miltenyi ◽  
Paulo Gaspar ◽  
Nuno Sousa ◽  
...  

We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.

Cardiology ◽  
2019 ◽  
Vol 144 (3-4) ◽  
pp. 125-130 ◽  
Author(s):  
Daniela Marisa Carvalho Silva ◽  
Nuno Marques ◽  
Olga Azevedo ◽  
Gabriel Miltenberger-Miltenyi ◽  
Dina Bento ◽  
...  

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.


2014 ◽  
Vol 111 (2) ◽  
pp. S99 ◽  
Author(s):  
Bouwien Smid ◽  
Linda van der Tol ◽  
Franco Cecchi ◽  
Perry Elliott ◽  
Derralynn Hughes ◽  
...  

2021 ◽  
Vol 10 (13) ◽  
pp. 2864
Author(s):  
Aleksandra Gamrat ◽  
Katarzyna Trojanowicz ◽  
Michał A. Surdacki ◽  
Aleksandra Budkiewicz ◽  
Adrianna Wąsińska ◽  
...  

Traditional electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), introduced in the pre-echocardiographic era of diagnosis, have a relatively low sensitivity (usually not exceeding 25–40%) in detecting LVH. A novel Peguero-Lo Presti ECG-LVH criterion was recently shown to exhibit a higher sensitivity than the traditional ECG-LVH criteria in hypertension. Our aim was to test the diagnostic ability of the novel Peguero-Lo Presti ECG-LVH criterion in severe aortic stenosis. We retrospectively analyzed 12-lead ECG tracings and echocardiographic records from the index hospitalization of 50 patients with isolated severe aortic stenosis (mean age: 77 ± 10 years; 30 women and 20 men). Exclusion criteria included QRS > 120 ms, bundle branch blocks or left anterior fascicular block, a history of myocardial infarction, more than mild aortic or mitral regurgitation, and significant LV dysfunction by echocardiography. We compared the agreement of the novel Peguero-Lo Presti criterion and traditional ECG-LVH criteria with echocardiographic LVH (LV mass index > 95 g/m2 in women and >115 g/m2 in men). Echocardiographic LVH was found in 32 out of 50 study patients. The sensitivity of the Peguero-Lo Presti criterion in detecting LVH was improved (55% vs. 9–34%) at lower specificity (72% vs. 78–100%) in comparison to 8 single traditional ECG-LVH criteria. Additionally, the positive predictive value (77% vs. 72%), positive likelihood ratio (2.0 vs. 1.5), and odds ratio (3.2 vs. 2.4) were higher for the Peguero-Lo Presti criterion versus the presence of any of these 8 traditional ECG-LVH criteria. Cohen’s Kappa, a measure of concordance between ECG and echocardiography with regard to LVH, was 0.24 for the Peguero-Lo Presti criterion, −0.01–0.13 for single traditional criteria, and 0.20 for any traditional criterion. However, by the receiver operating characteristics (ROC) curve analysis, the overall ability to discriminate between patients with and without LVH was insignificantly lower for the Peguero-Lo Presti versus Cornell voltage as a continuous variable (area under the ROC curve: 0.65 (95% CI, 0.48–0.81) vs. 0.71 (0.55–0.86), p = 0.5). In conclusion, our preliminary results suggest a slightly better, albeit still low, agreement of the novel Peguero-Lo Presti ECG criterion compared to the traditional ECG-LVH criteria with echocardiographic LVH in severe aortic stenosis.


2016 ◽  
Vol 13 (5) ◽  
pp. 340-346 ◽  
Author(s):  
Martina Gaggl ◽  
Natalija Lajic ◽  
Georg Heinze ◽  
Till Voigtländer ◽  
Raute Sunder-Plassmann ◽  
...  

2019 ◽  
Vol 83 (9) ◽  
pp. 1901-1907 ◽  
Author(s):  
Satoshi Yamashita ◽  
Masao Saotome ◽  
Hiroshi Satoh ◽  
Jun Kajihara ◽  
Yusaku Mochizuki ◽  
...  

2019 ◽  
Vol 73 (9) ◽  
pp. 766
Author(s):  
Alex Pui-Wai Lee ◽  
Josie T.Y. Chow ◽  
Kevin K.H. Kam ◽  
Yiting Fan ◽  
David Chan ◽  
...  

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