scholarly journals Fabry Disease and the Effectiveness of Enzyme Replacement Therapy (ERT) in Left Ventricular Hypertrophy (LVH) Improvement: A Review and Meta-Analysis

2022 ◽  
Vol 19 (1) ◽  
pp. 126-131
Author(s):  
Chung-Lin Lee ◽  
Shuan-Pei Lin ◽  
Dau-Ming Niu ◽  
Hsiang-Yu Lin
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Ventricular Hypertrophy ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Enzyme Replacement

Fabry Disease

2016 ◽  
Author(s):  
Michael West ◽  
Gabor Linthorst
Keyword(s):  
Natural History ◽  
Left Ventricular Hypertrophy ◽  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Patient Outcomes ◽  
Ventricular Hypertrophy ◽  
Unknown Origin ◽  
Left Ventricular ◽  
Enzyme Replacement ◽  
Modest Effect

Fabry disease was initially believed to be a very rare disorder, but an increase in prevalence following screening studies revealed that it may be more frequent in a less severe (nonclassical) variant. The adult physician can encounter both phenotypes: classical disease arising in childhood, or after establishing the diagnosis in an adult male. The nonclassical phenotype is usually diagnosed after additional investigations in a patient with renal disease or left ventricular hypertrophy (LVH) of unknown origin. Enzyme replacement therapy (ERT) appears to have a modest effect in Fabry disease, and many challenges remain both in understanding the pathophysiology and natural history as well as in improving patient outcomes.

scholarly journals P799 The echocardiographic and clinical characteristics of Fabry patients without overt left ventricular hypertrophy but progressing despite on enzyme replacement therapy

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S Y Lee ◽  
S H Lee ◽  
Y H Park
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Antibody Formation ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Enzyme Replacement ◽  
Tertiary Center ◽  
Group 2 ◽  
Group 1

Abstract Background Fabry disease (FD) is X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α- galactosidase. When the heart is involved, progressive left ventricular hypertrophy (LVH) is the key feature. Although, LVH is not present in all subjects, some of them progress with LVH despite enzyme replacement therapy (ERT). The present study aimed to evaluate the characteristics of patient of FD without overt LVH, but progresses with their left ventricular mass index (LVMI). Method : This study includes subjects carrying genetic mutations for FD without LVH (n = 12) in a single tertiary center. ‘Decreasing LVMI group (Group1)’ was defined when pre-ERT LVMI minus last LVMI value obtained by echocardiography was positive, and when negative, defined as ‘Increasing LVMI group (Group 2)’. The baseline characteristics and echocardiographic parameters including global strain was analyzed. Result : Total 6 patients were classified as Group 1 and 2 each. The median age at diagnosis for male was 21 vs 27 for each group, and 21 vs 31 for female. The median follow-up duration was 4.0 vs 5.7 yr. The antibody formation for replaced enzyme was 3 for Group 2 and any family member who developed overt LVH was much 1 vs 3 for group 1 vs 2. Initial 3 plane GLS was worse and showed trend to drop in Group 2. Conclusion : In the Fabry patients get worse with their LVMI but still not developed overt LVH despite enzyme replacement therapy, there are some clinical and echo-parameter difference. These findings could suggest insufficient enzyme replacement therapy. Group 1 (n = 6) Group 2 (n = 6) Female/Male 4/2 3/3 Age of at Dx (Female) (median) 21 28 Age of at Dx (Male) (median) 21 31 F/U duration (median) 4.0 yrs 5.7 yrs Antibody formation 0 3 Any Overt LVH family Genotype c.56T > C c.40-11T > A, 782_delG, c.658C > T Initial LVMI (Median) 98.2g/m2 70.9g/m2 Initial GLS (3P) -19 -17.8 Continuously elevated LysoGb3 2 4 Proteinuria >300mg 1 3 (1 preparing HD)

scholarly journals Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

2020 ◽  
Vol 28 (12) ◽  
pp. 1662-1668 ◽  
Author(s):  
Eleonora Riccio ◽  
◽  
Mario Zanfardino ◽  
Lucia Ferreri ◽  
Ciro Santoro ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Treatment Options ◽  
Real Life ◽  
Left Ventricular ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Neurologic Function

AbstractThe treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18–66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.

P0067PREDICTORS OF LONG-TERM OUTCOME IN A SPANISH COHORT OF PATIENTS WITH FABRY DISEASE ON ENZYME REPLACEMENT THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marian Goicoechea ◽  
Francisco Gomez-Preciado ◽  
Silvia Benito ◽  
Joan Torras ◽  
Roser Torra ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Left Ventricular ◽  
Response To Therapy ◽  
Clinical Event ◽  
Enzyme Replacement ◽  
Clinical Events ◽  
The Impact

Abstract Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p&lt;0.001) than males (logRank: 3.442, p=0.064). Lower baseline eGFR was associated with a 3- to 7-fold increase in the risk of clinical events in different Cox models. Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease

Cardiology ◽  
2019 ◽  
Vol 144 (3-4) ◽  
pp. 125-130 ◽  
Author(s):  
Daniela Marisa Carvalho Silva ◽  
Nuno Marques ◽  
Olga Azevedo ◽  
Gabriel Miltenberger-Miltenyi ◽  
Dina Bento ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Fabry Disease ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Gene Variants ◽  
Fabry Patient ◽  
Enzyme Replacement ◽  
Disease Awareness ◽  
Classic Phenotype ◽  
Gla Gene

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.

scholarly journals Enzyme replacement therapy for Fabry disease: a systematic review and meta-analysis

2012 ◽  
Vol 35 (4 suppl 1) ◽  
pp. 947-954 ◽  
Author(s):  
Taciane Alegra ◽  
Filippo Vairo ◽  
Monica V. de Souza ◽  
Bárbara C. Krug ◽  
Ida V.D. Schwartz
Keyword(s):  
Systematic Review ◽  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Enzyme Replacement

scholarly journals La terapia enzimatica sostitutiva nella malattia di Fabry

2019 ◽  
Vol 31 (3) ◽  
pp. 197-200
Author(s):  
Letizia Roggero ◽  
Sara Auricchio ◽  
Federico Pieruzzi
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Igg Antibody ◽  
Enzyme Replacement ◽  
Gi Symptoms

Enzyme Replacement Therapy for Fabry Disease Anderson-Fabry disease (FD) is a X-linked lysosomal storage disorder, which involves glycosphingolipids metabolism. Specific treatment for FD has been available in the last two decades, after the development and commercialization of recombinant human alfa-galactosidase A. Since then enzyme replacement therapy (ERT) has changed the natural history of the disease. Two different enzymatic formulations are available: agalsidase alfa and agalsidase beta at different dosages. The safety and efficacy profiles are similar. ERT induces Gb3 deposits reduction in renal and cardiac biopsies, improves quality of life, reduces pain and GI symptoms, decreases left ventricular mass and slows down renal function decline. In case of organ involvement, clinical evidence confirms the need to treat all patients with enzyme therapy, both male and female. In all other clinical settings, the decision to start ERT is controversial, because of the extremely variable clinical manifestations of FD. However, data suggest a greater response to ERT if started as early as possible in any patients. Timely treatment appears to be effective in stabilizing and possibly delaying FD progression. ERT infusion reactions due to allergic hypersensitivity or IgG antibody development could occur but can be easily managed. In-hospital and at home infusions are possible. The wide genetic and phenotypic heterogeneity observed in all FD patients requires a tailored approach to treatment options. Patients should be referred to an expert multidisciplinary team for the long term management of this challenging disease.

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