scholarly journals Fabry disease, do we think enough about this multisystemic disorder?: A presentation of three cases in a Serbian family

2012 ◽  
Vol 69 (7) ◽  
pp. 620-622
Author(s):  
Dejan Sakac ◽  
Goran Koracevic ◽  
Tatjana Pavlica ◽  
Slobodan Sekulic
Keyword(s):  
Case Report ◽  
Early Diagnosis ◽  
Fabry Disease ◽  
Storage Disease ◽  
Cerebrovascular Disorders ◽  
Organ Damage ◽  
Lysosomal Storage ◽  
Intracellular Accumulation ◽  
Enzyme Replacement ◽  
Possible Cause

Background. Fabry Disease is a rare, X-chromosomal inherited lysosomal storage disease with a consequent intracellular accumulation of neutral glycosphingolipids in various tissues. This can cause skin and ocular lessions, progressive renal, cardiac or cerebrovascular disorders. If a person in a family has Fabry disease, other family members including even extended relatives, may also be at risk. Case report. We presented three cases pointed out various manifestation of Fabry disease, that illustrate a possible cause for otherwise unexplained cardiac hypertrophy and various rhythm and conduction abnormalities. Conclusion. Although most symptoms begin in childhood, various manifestations often lead to misdiagnosis and clinical diagnosis is frequently delayed for many years, even decades. Enzyme replacement therapy has become available, pointing out the importance of early diagnosis so that treatment can be initiated before irreversible organ damage.

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.

scholarly journals Anderson-Fabry Disease in Females

2015 ◽  
Vol 12 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Petar Kes ◽  
Vesna Furic-Curko ◽  
Nikolina Basic-Jukic
Keyword(s):  
Fabry Disease ◽  
Lysosomal Storage Disease ◽  
Lysosomal Enzyme ◽  
Storage Disease ◽  
Signs And Symptoms ◽  
Organ Damage ◽  
Enzyme Deficiency ◽  
Diagnostic Approach ◽  
Lysosomal Storage ◽  
Globotriaosyl Ceramide

AbstractAnderson-Fabry disease (AFD) is the second most common lysosomal storage disease. This is an X-linked disorder due to lysosomal enzyme deficiency of a-galac-tosidasae A, that results in accumulation of globotriaosyl-ceramide in various tissues leading to organ damage, and resulting in a variety of cardiovascular, renal, neural, der-matological, psychological signs and symptoms. Despite being X-linked, heterozygous females can suffer from symptoms equally severe as male hemizygotes. This paper presents signs, symptoms, specific diagnostic approach and treatment possibilities of AFD in female patients.

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.

Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995–2017

2018 ◽  
Vol 55 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Dana Doheny ◽  
Ram Srinivasan ◽  
Silvere Pagant ◽  
Brenden Chen ◽  
Makiko Yasuda ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Storage Disease ◽  
Enzyme Assays ◽  
Lysosomal Storage ◽  
Pathogenic Mutations ◽  
Online Databases ◽  
Prevalence Estimates ◽  
Mutation Analyses

BackgroundFabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A (GLA) mutations, results in two major subtypes, the early-onset Type 1 ‘Classic’ and the Type 2 ‘Later-Onset’ phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised ‘benign/likely-benign’ variants, thereby inflating prevalence estimates.MethodsOnline databases were searched for all FD screening studies in high-risk clinics (1995–2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined.ResultsOf 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype.ConclusionsCompared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees.

Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis

2013 ◽  
Vol 66 (11) ◽  
pp. 918-923 ◽  
Author(s):  
Tim Reynolds
Keyword(s):  
Enzyme Activity ◽  
Cholesteryl Ester ◽  
Storage Disease ◽  
Treatment Options ◽  
Failure To Thrive ◽  
Early Death ◽  
Dried Blood Spots ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Reduced Activity

Cholesteryl ester storage disease (CESD) is an autosomal recessive lysosomal storage disorder caused by a variety of mutations of the LIPA gene. These cause reduced activity of lysosomal acid lipase, which results in accumulation of cholesteryl esters in lysosomes. If enzyme activity is very low/absent, presentation is in infancy with failure to thrive, malabsorption, hepatosplenomegaly and rapid early death (Wolman disease). With higher but still low enzyme activity, presentation is later in life with hepatic fibrosis, dyslipidaemia and early atherosclerosis.Identification of this rare disorder is difficult as it is essential to assay leucocyte acid phosphatase activity. An assay using specific inhibitors has now been developed that facilitates measurement in dried blood spots. Treatment of CESD has until now been limited to management of the dyslipidaemia, but this does not influence the liver effects. A new enzyme replacement therapy (Sebelipase) has now been developed that could change treatment options for the future.

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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