Nonsense Mutation in Exon 2 of the α-Galactosidase A Gene in a Patient with Fabry Disease

2001 ◽  
pp. 223-228
Author(s):  
E. Manni ◽  
A. Fogli ◽  
F. Baldinotti ◽  
S. Rossi ◽  
N. Funel ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Nonsense Mutation ◽  
Exon 2 ◽  
Alpha Galactosidase

Treatment of Anderson-Fabry Disease

2020 ◽  
Vol 26 (40) ◽  
pp. 5089-5099 ◽  
Author(s):  
Irene Simonetta ◽  
Antonino Tuttolomondo ◽  
Mario Daidone ◽  
Salvatore Miceli ◽  
Antonio Pinto
Keyword(s):  
Fabry Disease ◽  
Treatment Strategies ◽  
Signs And Symptoms ◽  
Current Treatment ◽  
Viral Gene ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Cell Based Therapy ◽  
Organ Manifestations ◽  
Alpha Galactosidase

: Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstration of the absence of or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females. Measurement of the biomarkers Gb3 and Lyso Gb3 in biological specimens may facilitate diagnosis. The current treatment of Anderson-Fabry disease is represented by enzyme replacement therapy (ERT) and oral pharmacological chaperone. Future treatments are based on new strategic approaches such as stem cell-based therapy, pharmacological approaches chaperones, mRNA therapy, and viral gene therapy. : This review outlines the current therapeutic approaches and emerging treatment strategies for Anderson-Fabry disease.

scholarly journals Lentivirus-mediated gene therapy for Fabry disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aneal Khan ◽  
Dwayne L. Barber ◽  
Ju Huang ◽  
C. Anthony Rupar ◽  
Jack W. Rip ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Bone Marrow Cells ◽  
Adult Males ◽  
Serious Adverse Events ◽  
Hematopoietic Stem ◽  
Primary Endpoints ◽  
Preparative Regimen ◽  
Post Infusion ◽  
Alpha Galactosidase

AbstractEnzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy.

scholarly journals Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease.

1987 ◽  
Vol 262 (5) ◽  
pp. 2062-2065
Author(s):  
P. Lemansky ◽  
D.F. Bishop ◽  
R.J. Desnick ◽  
A. Hasilik ◽  
K. von Figura
Keyword(s):  
Fabry Disease ◽  
Human Fibroblasts ◽  
Synthesis And Processing ◽  
Alpha Galactosidase

scholarly journals The Cardiovascular Phenotype in Fabry Disease: New Findings in the Research Field

2021 ◽  
Vol 22 (3) ◽  
pp. 1331
Author(s):  
Daniela Sorriento ◽  
Guido Iaccarino
Keyword(s):  
Fabry Disease ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Research Field ◽  
Cardiac Cell ◽  
Lysosomal Storage ◽  
Clinical Level ◽  
New Findings ◽  
Alpha Gene ◽  
Alpha Galactosidase

Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD’s development and progression that could become useful targets for therapeutics. This review discusses FD’s cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage.

scholarly journals Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant

2016 ◽  
Vol 11 (1) ◽  
Author(s):  
Malte Lenders ◽  
Frank Weidemann ◽  
Christine Kurschat ◽  
Sima Canaan-Kühl ◽  
Thomas Duning ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Alpha Galactosidase

scholarly journals Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease

PLoS Genetics ◽  
2013 ◽  
Vol 9 (8) ◽  
pp. e1003632 ◽  
Author(s):  
Jan Lukas ◽  
Anne-Katrin Giese ◽  
Arseni Markoff ◽  
Ulrike Grittner ◽  
Ed Kolodny ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Classification System ◽  
New Classification ◽  
Functional Characterisation ◽  
Alpha Galactosidase

scholarly journals Ocular findings in Fabry disease in Colombian patients

Biomédica ◽  
2019 ◽  
Vol 39 (3) ◽  
pp. 434-439 ◽  
Author(s):  
Katherine Rothstein ◽  
Jubby M. Gálvez ◽  
Ángela M. Gutiérrez ◽  
Laura Rico ◽  
Eveling Criollo ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Multidisciplinary Treatment ◽  
Case Series ◽  
Clinical History ◽  
Diagnosis And Treatment ◽  
Ophthalmologic Examination ◽  
Alpha Galactosidase ◽  
Prompt Diagnosis ◽  
Ocular Signs

Fabry disease is a rare X-linked disorder caused by an alpha-galactosidase enzyme deficiency, which leads to a progressive lysosomal glycosphingolipids accumulation, mainly globotriaosylceramide, in multiple organism tissues including the eye.This case series describes the first ophthalmological Colombian report of Fabry disease highlighting the importance of ocular signs as markers of the disease, useful in diagnosis and treatment to avoid long-term complications that lead to a morbi-mortality increment.We describe five cases of Fabry disease from Bogotá, Colombia, including a complete clinical history, ophthalmologic, optometric examination, and photographs. We found that all patients had refractive defects and that in all cases corneal verticillata pattern was found. Four patients presented with posterior capsule lens brown-beige deposits and four patients had conjunctival and retinal tortuous vessels. A complete ophthalmologic examination is important for prompt diagnosis, which is key to starting a multidisciplinary treatment and reducing morbi-mortality.

scholarly journals Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e36373 ◽  
Author(s):  
Mehdi Namdar ◽  
Catherine Gebhard ◽  
Rafael Studiger ◽  
Yi Shi ◽  
Pavani Mocharla ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Fabry Disease ◽  
Alpha Galactosidase
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