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<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.

MO061IS THE PM290I MUTATION RELATED TO ORGAN INVOLVEMENT OF FABRY DISEASE?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Francisca Silva ◽  
Nicole Pestana ◽  
José Durães ◽  
Nuno Guimarães Rosa ◽  
Gil Silva
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Genetic Variant ◽  
Clinical Manifestations ◽  
Mutant Enzyme ◽  
Enzyme Replacement ◽  
Screening Study ◽  
Gla Gene

Abstract Background and Aims Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy improved the natural course of this disease, but an early diagnosis is crucial for a successful treatment. Method A screening study for GLA gene mutations was conducted for all patients under dialysis, from a single centre. All the probands with a detectable mutation were analysed individually. Data on the patient's family and personal pathological history were retrospectively collected, by consulting the clinical file. Results 35 years-old female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite optimal medical treatment the disease progressed, and she started renal replacement therapy with peritoneal dialysis. Five years later she was enrolled in a pilot screening study for FD and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon 6 of the GLA gene was found. The proband didn’t meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index, a new ischemic cerebral lesion and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to the decision to initiate enzyme replacement therapy. Until now there are only a few descriptions of this genetic variant in the scientific literature. A Portuguese study analysed a total of 11 FD patients and described 2 patients with p.M290I mutation, without detectable Gb3 accumulation. Another study was designed to evaluate the genotype-phenotype relationship in 73 Chinese FD patients. Contrary to other reports, the p.M290I mutation was not associated to the classic FD phenotype. A Swiss investigation with a similar design analysed 69 FD patients during their routine annual examinations. M290I mutant enzyme was found in a 48-year-old heterozygous female with a classic FD phenotype but with a low serum LysoGb3. A Spanish newborn screening identified one male patient with FD and the p.M290I genetic variant but was unable to provide any information about the clinical expression of this mutation, since the diagnosis was made between the third and fifth days of life. The study describing the most patients carrying the M290I mutant enzyme is Brazilian and screened a total of 25,223 dialysis patients. Among 89 FD-positive patients, the p.M290I mutation was present in 22. However, the authors did not provide detailed information about the clinical manifestations or α-Gal A activity and LysoGb3 levels of these patients. Finally, a recent Portuguese screening of 150 hypertrophic cardiomyopathy patients found 25 patients with FD. Of these, one female carried the GLA gene variant p.M290I, with a non-detectable LysoGb3 plasma level. Conclusion We describe a case of FD due to a previously known but still poorly described GLA mutation, which offers strong evidence of its pathogenicity. To our knowledge, this is the first report of p.M290I mutation-associated disease activity evidenced by elevated levels of serum LysoGb3. Despite the absence of classic FD symptoms such as neuropathic pain, cornea verticillata and angiokeratoma, the presence of severe multiple organ evolvement, characterized by renal failure, cardiac disease and ischaemic stroke, strongly suggests a classic phenotype. Consequently, it is our opinion that the presence of a p.M290I GLA mutation should require a strict ongoing patient follow-up, as it may cause clinically significant disease.

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.

scholarly journals Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

2015 ◽  
Vol 27 (3) ◽  
pp. 952-962 ◽  
Author(s):  
Malte Lenders ◽  
Sima Canaan-Kühl ◽  
Johannes Krämer ◽  
Thomas Duning ◽  
Stefanie Reiermann ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Dose Reduction ◽  
Enzyme Replacement

scholarly journals White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up

2006 ◽  
Vol 64 (3b) ◽  
pp. 711-717 ◽  
Author(s):  
Laura B. Jardim ◽  
Flávio Aesse ◽  
Leonardo M. Vedolin ◽  
Cláudio Pitta-Pinheiro ◽  
João Marconato ◽  
...  
Keyword(s):  
White Matter ◽  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
White Matter Lesions ◽  
Resonance Imaging ◽  
Enzyme Replacement ◽  
Before And After ◽  
Magnetic Resonance Imaging Mri

PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.

scholarly journals Long-Term Effect of Enzyme Replacement Therapy with Fabry Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Manabu Komori ◽  
Yuika Sakurai ◽  
Hiromi Kojima ◽  
Toya Ohashi ◽  
Hiroshi Moriyama
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Enzyme Replacement ◽  
Hearing Acuity ◽  
Before And After ◽  
And Gender

Objective.To determine the effects of enzyme replacement therapy (ERT) on the hearing acuity in patients with Fabry disease.Materials.The study sample comprised 34 ears of 17 affected patients who underwent pure-tone audiometry before and after ERT.Methods.The patients were studied in relation to factors such as changes in hearing, presence of accompanying symptoms, status of renal and cardiac function, age, and gender. Data of pure-tone audiometry obtained before ERT and at the final examination were compared.Results.At the end of the follow-up period, no significant worsening of hearing acuity was noted at the end of the follow-up period. SSNHL was detected in 10 ears of 6 patients. Steroid therapy successfully cured the disease in 9 of the 10 ears.Conclusions.No significant worsening of hearing acuity was noted from the beginning to the end of ERT. The rate of improvement in SSNHL of Fabry disease was excellent in the treated patients. Hearing loss is a factor that causes marked deterioration of the patients’ quality of life, and it is desirable that the hearing acuity of patients be periodically evaluated and prompt treatment of SSNHL be administered, if available.

scholarly journals Clinical stability of Fabry disease in 54 months’ enzyme replacement therapy – follow-up of the first Polish study

2007 ◽  
Vol 117 (5-6) ◽  
pp. 260-265
Author(s):  
Stanisława Bazan-Socha ◽  
Tomasz Miszalski-Jamka ◽  
Paweł Petkow-Dimitrow ◽  
Jacek Musiał
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Enzyme Replacement ◽  
Polish Study ◽  
Clinical Stability

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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