scholarly journals Fabry Disease and Early Stroke

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
U. Feldt-Rasmussen
Keyword(s):  
Fabry Disease ◽  
White Matter Lesions ◽  
Vascular Endothelial ◽  
Lysosomal Storage ◽  
Mortality And Morbidity ◽  
Young Stroke ◽  
Enzyme Replacement ◽  
Hard Data ◽  
History Of ◽  
Corneal Opacities

Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses of results from ongoing studirs will add to the decision on whether or not to screen young stroke patients for Fabry disease. Finally, stroke prophylactic therapy should be used liberally in patients of both genders with verified Fabry disease. This includes primary prevention such as lifestyle counseling, targeting blood pressure, managing atrial fibrillation, diabetes mellitus, hyperlipidaemia, and ASA.

A Case of a 49-Year-Old Man with Nonclassical Fabry Disease Diagnosed by Renal Biopsy

Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Lanjun Fu ◽  
Peipei Zhang ◽  
Qingqing Ye ◽  
Manman Wu ◽  
Lingzhi He
Keyword(s):  
Fabry Disease ◽  
Renal Biopsy ◽  
Correct Diagnosis ◽  
Premature Mortality ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
St Segment ◽  
Major Organ ◽  
History Of ◽  
Gla Gene

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficiency of α-GLA activity, leading to major organ failure and premature mortality. According to different disease courses, FD can be divided into classical and nonclassical phenotypes. The nonclassical FD phenotype is always absent of characteristic symptoms, which makes identifying it challenging. This article presents a 49-year-old man with a 10-year history of proteinuria and decreased glomerular filtration rate. An electrocardiogram showed a complete right bundle branch block and abnormal Q waves in high lateral, accompanied by dramatically elevated ST segment. Consequently, a renal biopsy was performed. Vacuolation was found in many podocytes in light microscopic examinations. Similarly, a myelin-like structure was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, genetic analysis, p.R301Q (c.902G>A [p.Arg301Gln]), confirmed the FD diagnosis. Angiotensin receptor blocker and traditional Chinese medicine, but not enzyme replacement therapy, were prescribed due to financial constraints. The patient had stabilization of kidney disease 6 months later. The case showed that renal biopsy should be performed in patients with cardiac and renal symptoms, which could contribute toward the correct diagnosis for nonclassical FD type.

scholarly journals Fabry Disease Therapy: State-of-the-Art and Current Challenges

2020 ◽  
Vol 22 (1) ◽  
pp. 206
Author(s):  
Olga Azevedo ◽  
Miguel Fernandes Gago ◽  
Gabriel Miltenberger-Miltenyi ◽  
Nuno Sousa ◽  
Damião Cunha
Keyword(s):  
Fabry Disease ◽  
State Of The Art ◽  
Large Body ◽  
Real Life ◽  
Clinical Manifestations ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
New Therapies ◽  
Enzyme Replacement

Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that “in vitro” amenability may not always reflect “in vivo” amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.

scholarly journals Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

Diseases ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 2
Author(s):  
Maria L. Gonzalez Suarez ◽  
Charat Thongprayoon ◽  
Panupong Hansrivijit ◽  
Juan Medaura ◽  
Pradeep Vaitla ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Fabry Disease ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Graft Failure ◽  
Current Therapy ◽  
Transplant Recipients ◽  
Lysosomal Storage ◽  
Kidney Transplant Recipients ◽  
Enzyme Replacement

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

scholarly journals Fabry disease, a complex pathology not easy to diagnose

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Paolo Colomba ◽  
Simone Scalia ◽  
Giuseppe Cammarata ◽  
Carmela Zizzo ◽  
Daniele Francofonte ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Vascular Endothelium ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Lysosomal Storage ◽  
Familial Data ◽  
Enzyme Replacement ◽  
Cerebrovascular Complications ◽  
Cellular Events

Fabry disease is a multisystemic lysosomal storage disorder, inherited in an X-linked manner. It is a defect of metabolism of the glycosphingolipids, due to the reduction or absence of the activity of lysosomal enzyme α-galactosidase A. This reduction of activity causes the storage of globotriaosylceramide and derivatives in the lysosomes, triggering a cascade of cellular events, mainly in vascular endothelium. These events are the responsible for the systemic clinical manifestations and the renal, cardiac and cerebrovascular complications, or a combination of them. The symptomatology can lead to the premature death of patient between the fourth or fifth decade of life. The first symptoms can occur at different ages, generally in childhood, with different severity and course. Fabry disease is suspected on the basis of clinical and anamnestic-familial data, and it is confirmed by enzymatic and genetic assays. However, Fabry disease could be a pathology more complex than previously considered, and the diagnostic tests that are currently in use could be not always sufficient to confirm the clinical diagnosis. Probably, other factors could be also involved in the onset of symptomatology. In the last years, the knowledge of the disease is considerably increased but other studies are necessary to make a prompt and reliable diagnosis. An early diagnosis of Fabry disease is essential for the beginning of the enzyme replacement therapy, which can contribute to arrest its progression and improve the quality of life of patients.

scholarly journals Anderson–Fabry Disease: From Endothelial Dysfunction to Emerging Therapies

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Cosimo A. Stamerra ◽  
Rita Del Pinto ◽  
Paolo di Giosia ◽  
Claudio Ferri ◽  
Amirhossein Sahebkar
Keyword(s):  
Fabry Disease ◽  
Organ Damage ◽  
Lysosomal Storage ◽  
Messenger Ribonucleic Acid ◽  
Gene Therapies ◽  
Enzyme Replacement ◽  
Emerging Therapies ◽  
Life Threatening ◽  
Molecular Aspects ◽  
Partial Deficiency

The Anderson–Fabry disease is a rare, X-linked, multisystemic, progressive lysosomal storage disease caused by α-galactosidase A total or partial deficiency. The resulting syndrome is mainly characterized by early-onset autonomic neuropathy and life-threatening multiorgan involvement, including renal insufficiency, heart disease, and early stroke. The enzyme deficiency leads to tissue accumulation of the glycosphingolipid globotriaosylceramide and its analogues, but the mechanisms linking such accumulation to organ damage are only partially understood. In contrast, enzyme replacement and chaperone therapies are already fully available to patients and allow substantial amelioration of quality and quantity of life. Substrate reduction, messenger ribonucleic acid (mRNA)-based, and gene therapies are also on the horizon. In this review, the clinical scenario and molecular aspects of Anderson–Fabry disease are described, along with updates on disease mechanisms and emerging therapies.

Clinical Spectrum of Mucolipidosis Type IV

PEDIATRICS ◽  
1988 ◽  
Vol 81 (4) ◽  
pp. 602-602
Author(s):  
RAPHAEL WEITZ ◽  
GERTRUDE KOHN
Keyword(s):  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Motor Delay ◽  
Mucolipidosis Type Iv ◽  
Corneal Clouding ◽  
Type Iv ◽  
History Of ◽  
Corneal Opacities ◽  
Mucolipidosis Type

To the Editor.— We read with interest the presentation by Amir et al1 concerning the clinical spectrum and natural history of mucolipidosis type IV. Based on their experience with 20 patients, they try to provide guidelines for the clinical diagnosis of this lysosomal storage disease. It appears that severe visual impairment (due mainly to corneal opacities, myopia, and retinal degeneration) and psychomotor retardation are the cardinal features of this entity. However, corneal clouding and mild motor delay in their early stages may frequently be missed by even experienced pediatricians and we recently examined a 15-month-old boy who was referred to us for evaluation of a possible congenital myopathy.

scholarly journals Pregnancy Outcome after Exposure to Migalastat for Fabry Disease: A Clinical Report

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Natalja Haninger-Vacariu ◽  
Sarah El-Hadi ◽  
Udo Pauler ◽  
Marina Foretnik ◽  
Renate Kain ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Pregnancy Outcome ◽  
Fetal Mri ◽  
Hormonal Contraceptives ◽  
Clinical Report ◽  
Wild Type ◽  
Phase 3 ◽  
Recurrent Headache ◽  
Enzyme Replacement ◽  
History Of

Our patient was a 37-year-old woman with Fabry disease (GLA p.R112H) with a medical history of recurrent headache, nausea, vomiting, vertigo, and tobacco use (20 cigarettes/day). Fabry disease was diagnosed in 2005 when she experienced proteinuria, preeclampsia, and hypertension (201/130 mm Hg) during pregnancy (delivered 50 cm, 3.4 kg healthy boy; GLA wild type [WT]). Enzyme replacement therapy was initiated in 2009. The patient enrolled in the phase 3 ATTRACT trial (ClinicalTrials.gov; NCT01218659) and started migalastat in May 2012 while taking hormonal contraceptives. Two years after initiating migalastat, the patient had proteinuria (2166 mg/24 h) without hypertension (131/68 mm Hg), which persisted (788 mg/24 h a month later). Kidney biopsy results were consistent with existing Fabry disease. A serum pregnancy test and ultrasound confirmed pregnancy (18 weeks’ gestation). Migalastat and hormonal contraceptives were stopped; the patient continued to smoke. Fetal MRI was normal at ~29 weeks’ gestation. In October 2014, at 37+ weeks’ gestation, the patient delivered a 45-cm, 2.29-kg healthy girl (GLA WT). Excepting low birth weight, which may be related to the patient’s smoking, pregnancy outcome was normal despite exposure to migalastat for 18 weeks. Migalastat therapy during pregnancy is not advised.

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.

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):  
Treatment Options ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Igg Antibody ◽  
Enzyme Replacement ◽  
Gi Symptoms ◽  
History Of ◽  
Treat All

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.

scholarly journals First two years of reimbursed enzyme replacement therapy in the treatment of Fabry disease in Poland

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 841
Author(s):  
Michał Nowicki ◽  
Monika Komar ◽  
Mariusz Kusztal ◽  
Katarzyna Mizia-Stec ◽  
Tomasz Liberek ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Clinical Symptoms ◽  
Final Diagnosis ◽  
The Body ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Number Of Patients ◽  
Mean Time

Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene variants resulting in insufficient expression of α-galactosidase A. This enzyme deficiency leads to accumulation of globotriaosylceramide and globotriaosylsphingosine in plasma and in different cells throughout the body, causing major cardiovascular, renal, and nervous system complications. Until 2018, reimbursed enzyme replacement therapy (ERT) for FD was available in all European Union countries except Poland.             We present the preliminary results of the first two years of reimbursed ERT in Poland. We obtained data from the seven largest academic centers in Katowice, Kraków, Wrocław, Poznań, Gdańsk, Warszawa, and Łódź. The questionnaire included the following data: number of patients treated, number of patients qualified for ERT, and patient characteristics.             All centers returned completed questionnaires that included data for a total of 71 patients (28 men and 43 women) as of June 2021. Thirty-five patients with the diagnosis of FD confirmed by genetic testing (22 men and 13 women) had already qualified for reimbursed ERT. Mean (SD) age at the commencement of the ERT program was 39.6 (15.5) years (range 18-79 years). Mean time from the first clinical symptoms reported by the patients to the FD diagnosis was 21.1 (8.9) years, and the mean time from the final diagnosis of FD to the beginning of ERT was 4.7 (4.6) years.             FD is still underdiagnosed in Poland. To identify undiagnosed FD patients and to ensure that patients in Poland benefit fully from ERT, implementation of an effective nationwide screening strategy and close cooperation with a network of rare disease centers is advised.

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