scholarly journals Diverse phenotypic expression associated with the same genetic variant in female heterozygote patients of Anderson–Fabry disease: a case series

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Daisuke Tomioka ◽  
Koichi Kato ◽  
Tomoya Ozawa ◽  
Kenji Kodama ◽  
Hiroaki Takahashi ◽  
...  
Keyword(s):  
Coronary Angiography ◽  
Cardiac Hypertrophy ◽  
Fabry Disease ◽  
Genetic Variant ◽  
Case Series ◽  
Provocation Test ◽  
Woman Patient ◽  
Female Patients ◽  
Patient Number ◽  
Alpha Galactosidase

Abstract Background Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from a mutation of alpha-galactosidase A gene (GLA), causing deficiency in alpha-galactosidase activity. The enzyme deficit can lead to storage of globotriaosylceramide in various organs including heart. Studies suggest that vasospastic angina (VSA) is associated with AFD. Case summary This clinical case series aimed to present two female patients with AFD, including progressive cardiac involvement: a 50-year-old woman (patient number 1) and a 39-year-old woman (patient number 2) who are siblings with a male AFD patient harbouring p. Arg342Glu missense variant in alpha-galactosidase A gene (GLA), who suffered VSA and subsequent ventricular fibrillation. Enzymatic tests and genetic analysis confirmed AFD in both female patients and histological tests revealed globotriaosylceramide deposits in their hearts. In patient number 1, a 12-lead electrocardiography and transthoracic echocardiography revealed cardiac hypertrophy. Coronary angiography revealed no organic coronary artery stenosis and vasospasms was induced by spasm provocation test. In patient number 2, no signs of cardiac hypertrophy were found, and coronary arteries had no organic stenosis with negative spasm provocation test. Both patients received enalapril therapy and enzyme replacement therapy (ERT). Discussion Different phenotype of AFD was occurred even with the same genetic variant in female heterozygote patients. The duration of exposing accumulation of Gb3 might affect cardiac hypertrophy and vasospasms. Coronary angiography with acetylcholine provocation test should be considered in female AFD patient, especially in case with cardiac hypertrophy.

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.

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 Demographic Predictors of Concomitant Osteochondral Lesion of the Talus in Patients With Chronic Lateral Ankle Instability

2021 ◽  
Vol 6 (2) ◽  
pp. 247301142110133
Author(s):  
Yong Sang Kim ◽  
Tae Yong Kim ◽  
Yong Gon Koh
Keyword(s):  
Tilt Angle ◽  
Ankle Instability ◽  
Osteochondral Lesion ◽  
Case Series ◽  
Level Of Evidence ◽  
Lateral Ankle ◽  
Chronic Lateral Ankle Instability ◽  
Female Patients ◽  
Lateral Ankle Instability ◽  
Talar Tilt

Background: Osteochondral lesion of the talus (OLT) is commonly found as a concomitant pathologic lesion in a large proportion of patients with chronic lateral ankle instability (CLAI). This study investigated which characteristics in a patient with CLAI increase the risk for OLT. Methods: Three hundred sixty-four patients who underwent a modified Broström operation for their CLAI were reviewed retrospectively. The characteristics of each patient and variables associated with OLTs were investigated. Statistical analyses were performed to determine the effect of each potential predictor on the incidence of OLT, and to evaluate the associations between the patient characteristics and variables associated with OLTs. Results: Patients with OLTs were more frequently female (female vs male: 63.1% vs 43.9%, P = .003). In addition, the lesion sizes were larger in female patients (female vs male: 113.9 ± 24.9 mm2 vs 100.7 ± 18.0 mm2, P = .002), and medial lesions were more common in female patients (female vs male; 93.3% vs 81.8%, P = .036). The lesion sizes were larger in patients with a wider talar tilt angle ( P < .001), and patients with a medial OLT showed a wider talar tilt angle (12.0 ± 2.0 degrees vs 10.3 ± 2.2 degrees, P = .002). Conclusion: In this CLAI patient cohort, we found female patients to be at greater risk for OLTs than male patients. Furthermore, CLAI female patients with concomitant OLT had on average a larger lesion size, more frequent OLT medial position, and were associated with wider talar tilt angles, suggesting that females had more intrinsic ankle instability than males. Level of Evidence: Level IV, retrospective case series.

scholarly journals Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci
Keyword(s):  
Fabry Disease ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Female Patients ◽  
Maximal Wall Thickness ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

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
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