scholarly journals Fabry Cardiomyopathy: Current Practice and Future Directions

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1532
Author(s):  
Jeffrey Yim ◽  
Olivia Yau ◽  
Darwin F. Yeung ◽  
Teresa S. M. Tsang
Keyword(s):  
Fabry Disease ◽  
Early Stage ◽  
Point Of Care ◽  
Left Ventricular ◽  
The Body ◽  
Cardiac Biomarkers ◽  
Dried Blood Spot ◽  
Point Of Care Ultrasound ◽  
Enzyme Replacement ◽  
Blood Spot

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. Cardiac biomarkers, point-of-care dried blood spot testing, and advanced imaging modalities including echocardiography with strain imaging and magnetic resonance imaging (MRI) with T1 mapping now allow us to detect Fabry cardiomyopathy much more effectively than in the past. While enzyme replacement therapy (ERT) has been the mainstay of treatment, several promising therapies are now in development, making early diagnosis of FD even more crucial. Ongoing initiatives involving artificial intelligence (AI)-empowered interpretation of echocardiographic images, point-of-care dried blood spot testing in the echocardiography laboratory, and widespread dissemination of point-of-care ultrasound devices to community practices to promote screening may lead to more timely diagnosis of FD. Fabry disease should no longer be considered a rare, untreatable disease, but one that can be effectively identified and treated at an early stage before the development of irreversible end-organ damage.

Agreement of dried blood spot lyso-Gb3 concentrations obtained from different laboratories in patients with Fabry disease

2020 ◽  
Vol 58 (11) ◽  
pp. e275-e278
Author(s):  
Constantin Gatterer ◽  
Martina Gaggl ◽  
Gerald Mundigler ◽  
Paulus Rommer ◽  
Senta Graf ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Dried Blood Spot ◽  
Blood Spot

scholarly journals LO042: Sonography in Hypotension and Cardiac Arrest (SHoC) - Hypotension: derivation of an evidence-based consensus algorithm for the integration of point of care ultrasound into resuscitation of hypotensive patients

CJEM ◽  
2016 ◽  
Vol 18 (S1) ◽  
pp. S44-S44 ◽  
Author(s):  
P. Atkinson ◽  
J. Bowra ◽  
J. Milne ◽  
M. Lambert ◽  
B. Jarman ◽  
...  
Keyword(s):  
Point Of Care ◽  
Disease Incidence ◽  
Left Ventricular ◽  
Consensus Algorithm ◽  
Professional Organizations ◽  
Clinical Indication ◽  
Point Of Care Ultrasound ◽  
International Consensus ◽  
Modified Delphi ◽  
Delphi Approach

Introduction: Point of care ultrasound has become an established tool in the initial management of patients with undifferentiated hypotension. Current established protocols (RUSH, ACES, etc) were developed by expert user opinion, rather than objective, prospective data. We wished to use reported disease incidence to develop an informed approach to PoCUS in hypotension using a “4 F’s” approach: Fluid; Form; Function; Filling. Methods: We summarized the incidence of PoCUS findings from an international multicentre RCT, and using a modified Delphi approach incorporating this data we obtained the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. The modified Delphi tool was developed to reach an international consensus on how to integrate PoCUS for hypotensive emergency department patients. Results: Rates of abnormal PoCUS findings from 151 patients with undifferentiated hypotension included left ventricular dynamic changes (43%), IVC abnormalities (27%), pericardial effusion (16%), and pleural fluid (8%). Abdominal pathology was rare (fluid 5%, AAA 2%). After two rounds of the survey, using majority consensus, agreement was reached on a SHoC-hypotension protocol comprising: A. Core: 1. Cardiac views (Sub-xiphoid and parasternal windows for pericardial fluid, cardiac form and ventricular function); 2. Lung views for pleural fluid and B-lines for filling status; and 3. IVC views for filling status; B. Supplementary: Additional cardiac views; and C. Additional views (when indicated) including peritoneal fluid, aorta, pelvic for IUP, and proximal leg veins for DVT. Conclusion: An international consensus process based on prospectively collected disease incidence has led to a proposed SHoC-hypotension PoCUS protocol comprising a stepwise clinical-indication based approach of Core, Supplementary and Additional PoCUS views.

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.

Tumour incidence in Fabry disease: A cross-sectional study

2019 ◽  
Vol 3 (2) ◽  
pp. 80-87
Author(s):  
Federica Rossi ◽  
Sara Auricchio ◽  
Agnese Binaggia ◽  
Vincenzo L’imperio ◽  
Fabio Pagni ◽  
...  
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Fabry Disease ◽  
Incidence Rate ◽  
Early Stage ◽  
Treatment Success ◽  
Significant Risk ◽  
Cancer Development ◽  
Cancer Prevalence ◽  
Enzyme Replacement

Background: Recently, a possible correlation between altered glycosphingolipid metabolism, that occurs in Fabry disease, and cancer development has been suggested. We analysed both incidence and prevalence of benign and malignant tumours in a Fabry patient cohort and compared them with the Italian general population. The analysis of major risk factors was performed. Methods: A total of 53 Fabry patients, followed by Nephrology Unit of San Gerardo Hospital (Monza, Italy), were retrospectively enrolled. Primary outcome was cancer development during the follow-up period (2007–2017). Cancer prevalence and incidence rate were calculated and compared to those in the Italian general population, acquired from public report on cancer estimates produced by the Cancer Registers’ Italian Association. Fisher’s exact test and multivariate analysis were performed to identify significant risk factors. Results: Nine (17%) patients were diagnosed with malignant neoplasia (stage T1–T3, N0M0). Most of them were female (77.8%) and were 59 ± 9 years old. In the benign tumour group, different lesions, ranging from adenoma to dysplasia, were recorded. Italian cancer prevalence is currently 5.5%, while in our population it was 17%; the incidence rate ratio of the Fabry population compared with the general population was 2.66 (95% confidence interval from 1.33 to 5.32). The risk factor analysis has revealed that older age was a negative factor for cancer onset, while enzyme replacement therapy had a protective role effect against cancer in Fabry patients. Conclusion: Cancer could be an important associated pathology in Fabry patients. Their altered glycosphingolipid metabolism may have an oncogenic role. Further studies are needed to clarify the relationships between Fabry disease and cancer onset. Tumours in Fabry subjects could be diagnosed at an early stage allowing patients to have a concrete chance of treatment success.

scholarly journals Cell Transplantation Combined with Recombinant Collagen Peptides for the Treatment of Fabry Disease

2020 ◽  
Vol 29 ◽  
pp. 096368972097636
Author(s):  
Daisuke Kami ◽  
Masashi Yamanami ◽  
Takahiro Tsukimura ◽  
Hideki Maeda ◽  
Tadayasu Togawa ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cell Transplantation ◽  
Financial Burden ◽  
Kidney Injury ◽  
The Body ◽  
Term Survival ◽  
Enzyme Replacement ◽  
Continuous Release ◽  
Alpha Galactosidase

Fabry disease is caused by a decrease in or loss of the activity of alpha-galactosidase, which causes its substrates globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to accumulate in cells throughout the body. This accumulation results in progressive kidney injury due to glomerulosclerosis and in heart failure due to hypertrophy. Enzyme replacement therapy (ERT) has been used as the standard therapy for Fabry disease, but it causes a significant financial burden, and regular administration is inconvenient for patients. Because of the short half-life of alpha-galactosidase in vivo, therapeutic methods that can supplement or replace ERT are expected to involve continuous release of alpha-galactosidase, even at low doses. Cell transplantation therapy is one of these methods; however, its use has been hindered by the short-term survival of transplanted cells. CellSaic technology, which utilizes cell spheroids that form after cells are seeded simultaneously with a recombinant collagen peptide scaffold called a μ-piece, has been used to improve cell survival upon implantation. In this study, syngeneic murine embryonic fibroblasts were used to generate CellSaic that were transplanted into Fabry mice. These spheroids survived for 28 days in the renal subcapsular space with forming blood vessels. These results indicate CellSaic technology could be a platform to promote cellular graft survival and may facilitate the development of cell transplantation methods for lysosomal diseases.

scholarly journals Determinants of cerebral radiological progression in Fabry disease

2020 ◽  
Vol 91 (7) ◽  
pp. 756-763 ◽  
Author(s):  
Simon Körver ◽  
Maria G F Longo ◽  
Marjana R Lima ◽  
Carla E M Hollak ◽  
Mohamed El Sayed ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Fabry Disease ◽  
Cardiovascular Risk Factors ◽  
Clinical Characteristics ◽  
White Matter Lesions ◽  
Median Number ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Enzyme Replacement

Background and aimIt is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. The aim of this study was to determine the effect of ERT and clinical characteristics on progression of WMLs and infarctions on MRI in patients with FD.MethodsMRIs were assessed for WMLs (Fazekas scale), infarctions and basilar artery diameter (BAD). The effect of clinical characteristics (renal and cardiac involvement, cardiovascular risk factors, cardiac complications, BAD) and ERT on WML and infarction progression was evaluated using mixed models.ResultsOne hundred forty-nine patients were included (median age: 39 years, 38% men, 79% classical phenotype). Median follow-up time was 7 years (range: 0–13 years) with a median number of MRIs per patient of 5 (range: 1–14), resulting in a total of 852 scans. Variables independently associated with WML and infarction progression were age, male sex and a classical phenotype. Progression of WMLs and infarctions was not affected by adding ERT to the model, neither for the whole group, nor for early treated patients. Progression was highly variable among patients which could not be explained by other known variables such as hypertension, cholesterol, atrial fibrillation and changes in kidney function, left ventricular mass or BAD.ConclusionProgression of WMLs and cerebral infarctions in FD is mainly related to age, sex and phenotype. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible.

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