scholarly journals Fabry Cardiomyopathy: Current Treatment and Future Options

2021 ◽  
Vol 10 (14) ◽  
pp. 3026
Author(s):  
Irfan Vardarli ◽  
Manuel Weber ◽  
Christoph Rischpler ◽  
Dagmar Führer ◽  
Ken Herrmann ◽  
...  
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Alpha Galactosidase ◽  
Nerve System ◽  
Future Therapy ◽  
Reduced Activity

Fabry disease is a multisystem X-linked lysosomal storage disorder caused by a mutation in the alpha-galactosidase A gene. Deficiency or reduced activity of alpha-galactosidase A (GLA) is leading to progressive intracellular accumulation of globotriaosylceramide (GL3) in various organs, including the heart, kidney and nerve system. Cardiac involvement is frequent and is evident as concentric left ventricular hypertrophy. Currently, the standard treatment is enzyme replacement therapy or chaperone therapy. However, early starting of therapy, before myocardial fibrosis has developed, is essential for long-term improvement of myocardial function. For future treatment options, various therapeutic approaches including gene therapy are under development. This review describes the current and potential future therapy options for Fabry cardiomyopathy.

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 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.

Autopsy Findings of Heterozygous Fabry Disease with the Severe Phenotype: A Case Report

Nephron ◽  
2021 ◽  
pp. 1-6
Author(s):  
Maki Hiratsuka ◽  
Katsushi Koyama ◽  
Makoto Ito ◽  
Ryo Sato ◽  
Kodai Suzuki ◽  
...  
Keyword(s):  
Renal Failure ◽  
Fabry Disease ◽  
Cerebral Hemorrhage ◽  
Lysosomal Storage ◽  
Severe Phenotype ◽  
Autopsy Findings ◽  
Enzyme Replacement ◽  
Alpha Galactosidase ◽  
End Stage

Fabry disease (FD) is an inherited X-linked lysosomal storage disorder, with hemizygous males being more severely affected than heterozygous females. Herein, we report a rare case of FD in a heterozygous female with a severe phenotype. The patient had obesity and hyperlipidemia and had her first cerebral infarction at the age of 33 years. She underwent renal biopsy and was diagnosed with FD with morphological features of focal segmental glomerulosclerosis nephropathy at the age of 34 years. Her leukocyte alpha-galactosidase A activity was 2.3 Agal/U (normal: >20 Agal/U), and genetic analysis revealed the presence of the classical phenotype. Enzyme replacement therapy (ERT) was initiated at the age of 35 years; however, peritoneal dialysis owing to end-stage renal failure occurred at the age of 37 years. The patient died of a cerebral hemorrhage at the age of 44 years. Her Mainz Severity Score Index at the time of death was 48/76, suggestive of the severe phenotype. Autopsy findings revealed remarkable globotriaosylceramide accumulation on electron microscopy, particularly in the major organs and their vascular smooth muscle cells. Regarding the vertebral arteries which sourced the cerebral hemorrhage, the effects of FD-induced vascular thickening and long-term renal failure-induced atherosclerosis were confirmed. Furthermore, the patient’s vascular sclerosis was modified with acquired factors such as lifestyle-related disease associated with obesity. We recommend intensified treatment for metabolic factors simultaneous with ERT to help in delaying the progression of FD.

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.

MICROSURGICAL TREATMENT OF SYMPTOMATIC SACRAL PERINEURIAL CYSTS

Neurosurgery ◽  
2007 ◽  
Vol 60 (6) ◽  
pp. 1059-1066 ◽  
Author(s):  
Dongsheng Guo ◽  
Kai Shu ◽  
Rudong Chen ◽  
Changshu Ke ◽  
Yanchang Zhu ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Treatment Options ◽  
Current Treatment ◽  
Cerebrospinal Fluid Leakage ◽  
Local Defect ◽  
Microsurgical Treatment ◽  
The Past ◽  
Return Visits

Abstract OBJECTIVE The aim of this study was to investigate the microsurgical results of symptomatic sacral perineurial cysts of 11 patients and to discuss the treatment options of the past 10 years. METHODS We retrospectively reviewed the records of 11 patients with symptomatic sacral perineurial cysts who underwent microsurgical treatment at Tongji Hospital, Huazhong University of Science and Technology from 1993 through 2006. The philosophy was to perform total or partial cyst wall removal, to imbricate the remaining nerve sheath if possible, and to repair local defect with muscle, Gelfoam (Pharmacia & Upjohn, Kalamazoo, MI), and fibrin glue. Patient outcomes were assessed by comparing the preoperative and postoperative examination results. The average follow-up time obtained from return visits to the neurosurgery clinic or by telephone questionnaires ranged from 2 months to 13 years. A literature search and analysis of current treatment options were performed. RESULTS Nine of the 11 patients (82%) experienced complete or substantial relief of their preoperative symptoms. One patient (Patient 4) experienced worsening of bladder dysfunction after surgery and recovered slowly to subnormal function during the subsequent 2 months. The symptoms of Patient 9 did not resolve, and magnetic resonance imaging showed that the cyst had reoccurred. The patient underwent reoperation 3 months later without any improvement. One patient (Patient 11) experience a cerebrospinal fluid leakage complication. Neither new postoperative neurological defects nor infection were observed in our series. In the literature, there are six different treatment options under debate and controversially discussed. CONCLUSION Microsurgical treatment yielded the best long-term resolution of patient symptoms to date and should be recommended to appropriately selected patients.

Current treatment options for the Failing Fontan Circulation

2022 ◽  
Vol 18 ◽  
Author(s):  
Bart. W. Driesen ◽  
Michiel Voskuil ◽  
Heynric B. Grotenhuis
Keyword(s):  
Myocardial Dysfunction ◽  
Fontan Procedure ◽  
Treatment Options ◽  
Fontan Operation ◽  
Current Treatment ◽  
Fontan Circulation ◽  
Protein Losing Enteropathy ◽  
Resistance Protein ◽  
Failing Fontan

Abstract: The Fontan operation was introduced in 1968. For congenital malformations where biventricular repair is not suitable, the Fontan procedure has provided a long-term palliation strategy with improved outcome compared to the initially developed procedures. Despite these improvements, several complications merely as a result of a failing Fontan circulation (including myocardial dysfunction, arrhythmias, increased pulmonary vascular resistance, protein losing enteropathy, hepatic dysfunction, plastic bronchitis and thrombo-embolism) will limit life-expectancy in this patient cohort. This review provides an overview of the most common complications of the Fontan circulation and the currently available treatment options.

scholarly journals Irreparable rotator cuff tears: Current treatment options

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Tristan Juhan ◽  
Michael Stone ◽  
Omid Jalali ◽  
Will Curtis ◽  
John Prodromo ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Reverse Shoulder Arthroplasty ◽  
Treatment Options ◽  
Current Treatment ◽  
Rotator Cuff Tears ◽  
Biceps Tenotomy ◽  
Common Causes ◽  
Cuff Repair ◽  
Term Data

Rotator cuff disease is one of the most common causes of shoulder pain, yet controversy still exists regarding treatment of “irreparable” tears. Nonoperative management, including physical therapy and steroid injections, should be reserved for those without significant pain or functional impairment. Debridement may be used for low-demand patients, and should be performed with partial cuff repair, subacromial decompression, and/or acromioplasty to maximize outcomes. Biceps tenotomy and/or tenodesis have been shown to reduce postoperative pain and improve satisfaction when performed in conjunction with rotator cuff repairs, with no difference in functional outcome comparatively. Tendon transfers have been advocated with the potential benefit to improve function and decrease pain. More recently, extracellular matrix and human-derived dermal allografts have been used off-label as patch grafts in irreparable tears. Superior capsular reconstructive techniques and subacromial balloon spacers serve a similar function by acting to depress the humeral head in a cuff-deficient shoulder, however long-term data is needed before widespread adoption of these procedures. Finally, reverse shoulder arthroplasty serves as a salvage option for low demand elderly patients.

scholarly journals The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1411 ◽  
Author(s):  
Brianna M. Naumchik ◽  
Ashish Gupta ◽  
Heather Flanagan-Steet ◽  
Richard A. Steet ◽  
Sara S. Cathey ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Treatment Options ◽  
Lysosomal Storage Diseases ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Lysosomal Storage ◽  
Hematopoietic Cell Transplant ◽  
Psychomotor Delay ◽  
Enzyme Replacement ◽  
Enzyme Defects

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders.

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