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)

Long-Term Follow-Up of Monoclonal Gammopathies in Gaucher Disease Patients on Enzyme Replacement Therapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3336-3336
Author(s):  
Jae H. Park ◽  
Allan F. Moore ◽  
David J. Kuter
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Monoclonal Gammopathies ◽  
Enzyme Replacement ◽  
Group 3 ◽  
Group 2 ◽  
Initiation Of Therapy ◽  
Group 1

Abstract Gaucher Disease is a lysosomal storage disease in which glucocerebroside accumulates in macrophages because of a deficiency of the lysosomal enzyme, β-glucocerebrosidase. Polyclonal and monoclonal gammopathies (MG) have been frequently associated with long-standing Gaucher Disease, and there have been reports suggesting an increased incidence of multiple myeloma (MM) in these patients. Chronic stimulation of the immune system secondary to progressive glucocerebroside storage and increased expression of cytokines such as Interleukin 6 have all been postulated to be the mechanism underlying this association. The purpose of this study was to ascertain the incidence and natural history of MG in Type 1 Gaucher Disease patients on enzyme replacement therapy (ERT) followed for up to 15 years. Twenty-eight patients with Type I Gaucher Disease on ERT seen at a single medical center were selected for the analysis. Of the twenty-eight patients, 17 (60.7%) were male; 11 (39.3%) were female; and the median age at the initiation of therapy was 42 years (range 25–85 years). Serum protein electrophresis (SPEP), immunofixation, and immunoglobulin quantitation were performed in all of these patients before initiating ERT and at intervals during follow-up. The patients were categorized into three groups based on their initial SPEP results: Group 1: those with normal SPEP pattern; Group 2: those with polyclonal gammopathy; and Group 3: those with MG. At the time of initiation of ERT, Group 1 contained 12 patients (42.8%) while Groups 2 and 3 each had 8 patients (28.6%). During follow up for a median of 8.5 years (range 1–15 years), 2 patients from the Group 1 (16.7%) and 4 patients from Group 2 (50%) developed MG. Of the patients in Group 3, 3 patients (21.4%) reverted to a normal SPEP pattern. Overall, 14 patients (50%) in all three groups had a MG identified at the time of initiation of therapy or during follow-up: 3 (all in Group 3) reverted to a normal SPEP pattern while the other 11 patients showed no change in M-spike levels after a median of 8.5 years of follow up. All 14 patients with MG had a monoclonal IgG immunoglobulin, and 3 of them also had a monoclonal IgM immunoglobulin. There was no association between the occurance or type of MG with any particular Gaucher Disease genotype, patient age, or other clinical variable. Only one of the patients developed a malignancy: an elderly man with MG developed Hodgkin’s Disease. None of our patients developed MM. In conclusion, these data confirm the high rate of MG in patients with Gaucher Disease but a low rate of progression to any other plasmacytic or lymphocytic disorder.

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 Left Ventricular Hypertrophy in Children and Adolescents on Chronic Renal Replacement Therapy

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 335A-335A
Author(s):  
Mark M Mitsnefes ◽  
Stephen R Daniels ◽  
C Frederic Strife ◽  
Philip Khoury ◽  
Steven Schwartz ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Left Ventricular Hypertrophy ◽  
Children And Adolescents ◽  
Replacement Therapy ◽  
Ventricular Hypertrophy ◽  
Left Ventricular

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.

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