Background: Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. Objective: This study aimed to assess the long-term effects of ERT with recombinant α-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Patients: Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). Results: At 45 months of treatment, LV mass and LV wall thickness had ...
Fabry Disease Market: Report. The primary disease process starts in infancy, or even as early as in the fetal stage of development. In FD, lysosomal storage and cellular dysfunction are believed to trigger a cascade of events including cellular death, compromised energy metabolism, small vessel injury, K(Ca) channel dysfunction in endothelial cells, oxidative stress, impaired autophagosome maturation, tissue ischemia and, importantly, development of irreversible cardiac and renal tissue fibrosis.. Fabry Disease Market: Classification. Fabry Disease is classified as the Type 1 classic and Type 2 later-onset on the basis of phenotype of the disease. Both sub-types result in renal failure, and/or cardiac disease, and early death. Type 2 later-onset Fabry Disease is more frequent as compared to Type 1 classic Fabry Disease.. Fabry Disease Market: Symptoms. Symptoms of the disorders like Schindler disease, Gaucher disease, Fucosidosis, Erythromelalgia can be similar to those of Fabry disease. Thus ...
TY - JOUR. T1 - Urinary podocyte loss is increased in patients with fabry disease and correlates with clinical severity of fabry nephropathy. AU - Fall, Brent. AU - Scott, C. Ronald. AU - Mauer, Michael. AU - Shankland, Stuart. AU - Pippin, Jeffrey. AU - Jefferson, Jonathan A.. AU - Wallace, Eric. AU - Warnock, David. AU - Najafian, Behzad. PY - 2016/12. Y1 - 2016/12. N2 - Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine ...
Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of a-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed a-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and ...
Journal: EJNMMI - European Journal of Nuclear Medicine and Molecular Imaging ArticleTitle: Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease
TY - JOUR. T1 - Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease. AU - Fervenza, Fernando C.. AU - Torra, Roser. AU - Warnock, David G.. PY - 2008/12/1. Y1 - 2008/12/1. N2 - Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry ...
Fabry disease is an inherited disorder. It follows an X-linked pattern of inheritance because the gene that makes alpha-Gal A is on the X chromosome. A chromosome is a package of genetic material, and humans have 23 pairs of chromosomes, which they inherit from their parents. The X-chromosome is one of the two chromosomes (X and Y) that determine an individuals sex. Males have one Y chromosome and one X-chromosome; for males with Fabry disease, the X-chromosome carries the defective a-Gal A gene. Females have two X chromosomes; for females with Fabry disease, one X-chromosome carries the defective a-Gal A gene and the other carries a normal, healthy a-Gal A gene. A male with Fabry disease will pass his X-chromosome with the defective alpha-Gal A gene onto each of his daughters, but to none of his sons. A female with Fabry disease has a 50% chance of passing the X-chromosome with the defective alpha-Gal A gene onto each of her children, both sons and daughters.. For more information, see: ...
Release: Dec. 4, 2002. Childrens Hospital of Iowa to test new treatment for Fabry disease. The Childrens Hospital of Iowa at University of Iowa Hospitals and Clinics will be one of 20 medical centers to take part in a major international study of a new treatment for Fabry disease, a rare genetic disorder that affects an estimated 1 in 40,000 males worldwide. The goal of the trial is to determine the safety and efficacy of recombinant human alpha-galactosidase A (Fabrazyme) on the progression of renal disease and significant clinical events in patients with Fabry disease. This will be a Phase IV multi-center, multinational, randomized, double-blind, placebo-controlled trial. Because Fabry disease is a rare genetic disorder, centers will need to work aggressively to identify patients to take part in this study. We will be working with families, Fabry patient organizations and medical centers throughout our area to identify patients for this very important clinical trial. We are very pleased to ...
Ramaswami, U., Parini, R., Pintos-Morell, G., Kalkum, G., Kampmann, C., Beck, M. and on behalf of the FOS Investigators (2012), Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey. Clinical Genetics, 81: 485-490. doi: 10.1111/j.1399-0004.2011.01671.x ...
BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Central nervous system (CNS) manifestations consist mainly of cerebrovascular events. Brain MRI results are often abnormal. Purpose: The aim of the study was to describe CNS involvement in a group of Italian patients with AFD. METHODS: Clinical and brain MRI data of 43 patients with AFD (25 men, 41.94+/-10.83 years old and 18 women, 52.48+/-17.50 years old) were analysed retrospectively. 17 male patients and 7 female patients were under treatment with enzyme replacement therapy (ERT). RESULTS: All 43 patients had signs or symptoms of AFD. 16 men (64%) and 13 women (72%) demonstrated CNS involvement, although with varying severity. Overall, 6 men and 5 women had suffered from cerebrovascular accidents with an age at onset of 33.64+/-13.65 years and 53.68+/-11.71 years, respectively. Brain MR images were abnormal in 16/25 men and in 13/16 women. During CNS monitoring, ...
People with Fabry Disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to break down and removes certain types of fatty substances called glycolipids. These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid (globatriaosylceramide or GL-3) levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study analyzed the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease that previously participated in the AGAL-008-00 (NCT0074984) study ...
Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of globotriaosylceramide ( GL-3) throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable. Fabry disease is often difficult to diagnose since signs and symptoms are often nonspecific.. Symptoms. Many symptoms associated with Fabry disease are nonspecific making it a difficult disease to diagnosis. Not all symptoms may appear nor develop in any particular order. However, younger patients may have some or all of the following:. ...
HCM and Fabry disease are distinct inherited disorders that can lead to myocardial hypertrophy. The initial treatment in obstructive HCM includes pharmacologic therapy. If symptoms cannot be controlled with pharmacotherapy, then patients have been offered dual chamber pacing, surgical septal myectomy, or catheter based septal ablation.. Isolated cardiac Fabry disease has been reported in 3-5% of patients with undifferentiated myocardial hypertrophy and in a similar proportion of patients referred for tertiary evaluation of HCM.3,4 Recently, Fabry disease has been shown to respond to enzyme replacement therapy, including an improvement in cardiac function and regression of hypertrophy.5. The implications of an incorrect diagnosis are considerable. If Fabry disease is misdiagnosed as HCM, patients could be denied treatment with enzyme replacement and exposed to the invasive treatment strategies for obstructive HCM, which have procedural mortality rates of 1-3%. Fortunately, none of the patients in ...
Enzyme replacement therapy can reduce storage, ease pain, and preserve organ function in some individuals with Fabry disease. Drugs are often prescribed to treat pain that accompanies Fabry disease but does not treat the disorder. The U.S. Food and Drug Administration has approved migalastat (Galafold) as an oral medication for adults with Fabry disease who have a certain genetic mutation. Anti-platelet medications can help prevent strokes and medications that lower blood pressure can slow the decline of kidney function in people with Fabry disease. ...
This is a global prospective observational study of women with Fabry disease and their infants during pregnancy and/or breastfeeding. The study will evaluate outcomes of pregnancy and/or breastfeeding in women and infants exposed to migalastat. All pregnant women with Fabry disease are eligible to enroll, an unexposed cohort potentially can be used for comparisons.. Cases will be reported voluntarily to the Pregnancy Coordinating Center (PCC) from any country by Healthcare Providers (HCPs), by patients and secondary contacts. The PCC will follow patients throughout their pregnancies and/or breastfeeding and infant through 1 year of age.. There will be 2 cohorts enrolled in the study. Cohort 1 will be pregnant and/or breastfeeding patients who have Fabry Disease, and have been exposed to at least 1 dose of migalastat during pregnancy and/or breastfeeding. Cohort 2 will be pregnant and/or breastfeeding patients who have Fabry Disease, who were not exposed to migalastat during pregnancy and/or ...
Fabry disease, Anderson-Fabry disease, Angiokeratoma corporis diffusum. Authoritative facts about the skin from DermNet New Zealand.
Mutations of the gene GLA influence the enzyme α-galactosidase A. These mutations can affect the synthesis,ref name=lemansky,Lemansky et al., Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease., J Biol Chem. 1987 Feb 15, PubMed,/ref,, kinetic properties and stability,ref name=bernstein,Bernstein et al., Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene., J Clin Invest 1989 Apr, PubMed,/ref, of the enzyme which leads to a decreased enzyme activity. Hence the catabolization of glycosphingolipids is not done properly which is especially the case for the breakdown of globotriaosylceramide (GL3) to lactosylceramide (GL2) and galactose (see Fig. 3 and 4),ref name=nance,Nance et al., Later-onset Fabry disease: an adult variant presenting with the cramp-fasciculation syndrome., Arch Neurol. 2006 Mar, PubMed,/ref,. Since the α-galactosidase A is located in the lysosome, Fabry ...
Mutations of the gene GLA influence the enzyme α-galactosidase A. These mutations can affect the synthesis,ref name=lemansky,Lemansky et al., Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease., J Biol Chem. 1987 Feb 15, PubMed,/ref,, kinetic properties and stability,ref name=bernstein,Bernstein et al., Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene., J Clin Invest 1989 Apr, PubMed,/ref, of the enzyme which leads to a decreased enzyme activity. Hence the catabolization of glycosphingolipids is not done properly which is especially the case for the breakdown of globotriaosylceramide (GL3) to lactosylceramide (GL2) and galactose (see Fig. 3 and 4),ref name=nance,Nance et al., Later-onset Fabry disease: an adult variant presenting with the cramp-fasciculation syndrome., Arch Neurol. 2006 Mar, PubMed,/ref,. Since the α-galactosidase A is located in the lysosome, Fabry ...
Fabry disease is an X-linked dominant condition that affects 1 in 40,000 to 60,000 males. The prevalence in females is unknown. [1] Fabry disease results from mutations in the GLA gene encoding alpha-galactosidase A. The inability to metabolize glycosphingolipids causes a buildup in globotriaosylceramide in the cells found in nerves, vasculature, and other tissues including the cornea. This is a systemic disease that commonly presents as numbness and tingling of the hands and feet (acroparesthesias), skin lesions (angiokeratomas), decreased sweating (hypohidrosis), gastrointestinal dysfunction, kidney dysfunction, heart disease, vascular disease, and the following ophthalmic findings: corneal verticillata and vascular tortuosity. [2]. Corneal verticillata was first reported by Gruber in 1946 but it was not until 1969 when verticillata was attributed to Fabry disease by Franceschetti et al. [3,4] Corneal verticillata are also associated with many medications that cause subepithelial deposits and ...
Background: Fabry disease. an X-linked deficiency of α-galactosidase A coded by the GLA gene, leads to intracellular globotriaosylceramide (GL-3) accumulation. Although less common than in males, chronic kidney disease, occurs in ~15% of females. Recent studies highlight the importance of podocyte injury in Fabry nephropathy development and progression. We hypothesized that the greater the % of podocytes with active wild-type GLA gene (due to X-inactivation of the mutant copy) the less is the overall podocyte injury. Methods: Kidney biopsies from 12 treatment-naive females with Fabry disease, ages 15 (8-63), median [range], years were studied by electron microscopy and compared with 4 treatment-naive male patients.. Results: In females, 51 (13-100)% of podocytes (PC) per glomerulus had no GL-3 inclusions, this consistent with a non-Fabry podocyte phenotype (NFPC). In PC with GL-3 inclusions [Fabry podocyte phenotype (FPC)], GL-3 volume density per podocyte was virtually identical in females and ...
Figure 1. Cardiac hypertrophy in a patient with Fabry disease. A. and B. Concentric LV hypertrophy. Note the presence of a hyperechogenic region in the posterior wall (mid-wall level, arrow), corresponding to localized fibrosis. C. Right ventricular free wall hypertrophy from subcostal view.. In most cases of FD, the LVH is concentric and non-obstructive; however, an asymmetrical hypertrophy with septal thickening and posterior wall fibrotic thinning may present in advanced cases. There have also been rare case reports of patients with obstructive forms of hypertrophic cardiomyopathy. The LVH is progressive in nature, and is rarely severe in children or adolescents. Of note, the echocardiographically derived cardiac mass is proportional to the electrocardiographic LVH low-voltage on the ECG, presenting an argument against Fabry disease in these patients.. Right ventricular (RV) hypertrophy is also common [9] (around 70% of Fabry patients display it) and may progress to RV dilation (Figure 1C). ...
RnRMarketResearch.com offers Fabry Disease - Pipeline Review, H1 2015global research report on its store.. This report provides comprehensive information on the therapeutic development for Fabry Disease, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Fabry Disease and special features on late-stage and discontinued projects.. Global Markets Directs report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Directs proprietary databases, Company/University websites, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources, put ...
Background- Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated.. Methods and Results- Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant α-Gal A (agalsidase β, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients ...
Introduction. Fabry disease is a rare genetic lysosomal storage disorder of glycosphingolipids with X-linked transmission and an estimated incidence of 1:40,000-1:117,000 live male births.1 Partial or complete deficiency of the enzyme alpha-galactosidase A (a-Gal A) results in altered metabolism and progressive lysosomal accumulation of the substrate (mostly globotriaosylceramide, Gb3).2 The responsible gene is located on the long arm of the chromosome X (Xq22). More than 600 mutations have been identified with variable phenotypical expression.3. Clinically we distinguish the classical form and two variants, cardiac and renal. In the classical form clinical manifestations appear during childhood or early adolescence including acroparesthesias, angiokeratomas and corneal opacities.4 Progressive accumulation of Gb3 in the kidneys, heart and central nervous system lead to renal failure, hypertrophic cardiomyopathy and cerebral vascular accidents limiting life expectancy. The cardiac variant of the ...
Fabry disease is a rare enzyme deficiency known as a lysosomal storage disease. Wikipedia The enzyme involved, alpha galactosidase A, is coded by the GLA gene. OMIM Although Fabry disease has been considered an X-linked recessive condition, female carriers of a single mutated GLA gene may have significant symptoms. Enzyme replacement therapy is helpful, although it is currently extremely expensive, and production problems have led to shortages of the drug. [1] ...
Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and …
Cardiac microvascular function abnormalities in Fabry patients have been demonstrated by measurements of myocardial blood flow and coronary flow reserve, an index of microvascular function.14 In addition, a survey of female Fabry patients revealed that cardiac ischemia could be confirmed by ECG and serological markers in the absence of coronary artery stenosis, suggesting that the ischemia in these patients was of microvascular origin.11 However, widespread coronary artery disease also has been documented in Fabry patients15 and noted at autopsy in a male patient who died of a massive myocardial infarction.16 In the present study, we characterized the baseline pathology of GL-3 accumulation in cardiac biopsies and demonstrated its successful clearance from the microvasculature after enzyme replacement therapy.. It has long been established that GL-3 is transported in low- and high-density lipoprotein particles17-19 and that vascular cells accumulate GL-3 from the circulation through the ...
TY - JOUR. T1 - Lack of susceptibility of cells from patients with Fabry disease to productive infection with R5 human immunodeficiency virus. AU - Lund, Nicole. AU - Branch, Donald R. AU - Sakac, Darinka. AU - Lingwood, Clifford A. AU - Siatskas, Christopher. AU - Robinson, Chevalia J. AU - Brady, Roscoe O. AU - Medin, Jeff. PY - 2005. Y1 - 2005. N2 - A lack of viral replication after HIV-1Ba-L (R5) but not HIV-1IIIB (X4) infection was found using in-vitro activated peripheral blood-derived mononuclear cells from patients with Fabry disease, who have a defect in the catabolism of globotriaosylceramide. CCR5, but not CD4 or CXCR4 expression levels, were lower and the surface expression of globotriaosylceramide was negligible on activated patients cells. Our findings suggest a novel resistance mechanism to productive infection with R5 HIV-1 that potentially involves abnormal globotriaosylceramide catabolism.. AB - A lack of viral replication after HIV-1Ba-L (R5) but not HIV-1IIIB (X4) infection ...
In this article, alpha-galactosidase A activity was assayed in newborn screening blood spots of Italian male neonates. This study revealed a high incidence of later-onset Fabry disease.. For more information on Fabry disease, see chapter 150 of OMMBID ...
Response:. We thank Drs Lidove, Joly, and Touzé1 for their interest in our publications with regard to screening for Fabry disease in stroke patients, and for their analysis of currently available epidemiological data.2,-,6. Several issues, however, preclude drawing solid conclusions from their meta-analysis. First, relevant heterogeneity in the study designs exists, especially with regard to the stroke subtype, the stroke etiology, and the demographic data, and even the screening methodology should be taken into account.2,4,5 Second, limiting screening for Fabry disease to cryptogenic stroke patients may result in selection bias because the condition is known to be associated with cerebral microangiopathy and macroangiopathy,7,8 cardioembolic phenomena,9 and coagulopathy.10 Finally, exclusion of patients with the D313Y mutation is debatable because this mutation has been identified in classically affected males.11. Obviously, additional data are mandatory to substantiate decision-making about ...
PUNE, India, September 7, 2015 /PRNewswire/ -- Fabry Disease Market - Risk Factors, Comorbidities/Manifestations, Epidemiological Trends and Fabry Disease...
Patients affected by a rare and potentially fatal inherited metabolic disorder called Fabry disease are now benefiting from a new treatment that researchers at Childrens Hospital of Iowa helped create.. Fabry disease affects approximately 5,000 people worldwide. The average lifespan of people diagnosed with the disorder is 50 years. The disease is caused by a deficiency of an enzyme called alpha-galactosidase A. Patients affected by the condition can develop kidney failure, strokes, heart disease and disabling pain. The Food and Drug Administration (FDA) recently approved a medication called Fabrazyme, produced by Genzyme General, for the treatment of Fabry disease. The therapy replaces the missing enzyme in order to help correct the disorder. The treatment took 30 years of research to develop.. Thomas Loew, M.D., associate professor (clinical) at Childrens Hospital of Iowa in University of Iowa Hospitals and Clinics, helped conduct the research that led to the FDAs approval of ...
PubMed journal article: Agalsidase alfa in pediatric patients with Fabry disease: a 6.5-year open-label follow-up study. Download Prime PubMed App to iPhone, iPad, or Android
The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for migalastat (Galafold) for the treatment of Fabry disease, a rare genetic disorder. Patients with Fabry disease do not have enough of an enzyme called alpha-galactosidase A.
Fabry disease is an X-linked recessive disorder that leads to the accumulation of a lipid called globotriaosylceramide in the cells of the body. The condition is rare and affects around 1 in 50,000 males. As an X-linked condition, Fabry disease mainly affects males, although females can also be affected.
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. In recent years, the prevalence of FD has been reported to be up to 4% in cryptogenic young stroke patients. However, there have been no population-based studies in unselected patients with transient ischaemic attack (TIA) or stroke across the full range of ages. METHODS: We determined the prevalence of FD mutations in consecutive patients from a population-based study of acute TIA or ischaemic stroke (Oxford Vascular Study). Analysis included amplifying of the α-galactosidase A gene by polymerase chain reaction, denaturing high-performance liquid chromatography (dHPLC) analysis and sequencing using standard automated sequencing protocols [Mutation Surveyor software (Softgenetics)] where the dHPLC indicated a possible mutation. RESULTS: Samples of 1046 consecutive patients (52% women; mean age 73.2 years; 15% age |60 years; 572 stroke; 474 TIA) were tested. No patient had a known
We developed a mass spectrometric procedure to quantify sphingosine-1-phosphate (S1P) in biological materials. The use of newly synthesized (13)C5 C18-S1P and commercial C17-S1P as internal standards rendered very similar results with respect to linearity, limit of detection and limit of quantitation. Caution is warranted with determination of plasma S1P levels. Earlier it was reported that S1P is elevated in plasma of Fabry disease patients. We investigated this with the improved quantification. No clear conclusion could be drawn for patient plasma samples given the lack of uniformity of blood collection and plasma preparation. To still obtain insight, plasma and tissues were identically collected from α-galactosidase A deficient Fabry mice and matched control animals. No significant difference was observed in plasma S1P levels. A significant 2.3 fold increase was observed in kidney of Fabry mice, but not in liver and heart. Comparative analysis of S1P in cultured fibroblasts from normal ...
Fabry disease is an X-linked condition that affects both men and women. The manifestations of this complex disease are progressive and multisystemic. The classic form is seen in both males and females, although the manifestations are often less severe in females and disease progression is generally delayed compared with males. This chapter describes the natural history of the classic form of the disease, as well as the different signs and symptoms in females, and atypical late-onset disease in males.
Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that ...
Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study ...
Introduction Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. Methods A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement. Results For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should ...
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Ninety-five of 121 (79%) adult patients and 11 of 16 (69%) pediatric patients (106 of 137, 74% of all patients) treated with Fabrazyme (agalsidase beta) in clinical studies have developed IgG antibodies to Fabrazyme (agalsidase beta) . Most patients who develop IgG antibodies do so within the first 3 months of exposure. IgG seroconversion in pediatric patients was associated with prolonged half-life of Fabrazyme (agalsidase beta) , a phenomenon rarely observed in adult patients [see CLINICAL PHARMACOLOGY and Use in Specific Populations]. A possible cause for this prolongation likely pertains to the ability of antibodies to act as carriers for their antigens. Among the 14 female patients exposed to Fabrazyme (agalsidase beta) in clinical studies, four (two adult and two pediatric patients) developed IgG antibodies to Fabrazyme (agalsidase beta) . IgG antibodies to Fabrazyme (agalsidase beta) were purified from 15 patients with high antibody titers ( ≥ 12,800) and studied for inhibition of in ...
Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Read More ...
Agalsidase beta is a man-made form of the naturally-occurring alpha-galactosidase A enzyme. A deficiency of this enzyme is called Fabry disease. Agalsidase beta reduces deposits of globotriaosylceramide (GL-3) in the kidneys and certain other cells in the body. Agalsidase beta is used in the treatment of Fabry disease...
TY - JOUR. T1 - Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy. AU - Chimenti, Cristina. AU - Scopelliti, Fernanda. AU - Vulpis, Elisabetta. AU - Tafani, Marco. AU - Villanova, Lidia. AU - Verardo, Romina. AU - De Paulis, Ruggero. AU - Russo, Matteo A.. AU - Frustaci, Andrea. PY - 2015/11/1. Y1 - 2015/11/1. N2 - Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of α-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry. Western blot analysis for nitrotyrosine was also performed. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), whereas apoptosis was ...
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme
Answer: The major manifestations of Fabry disease in hemizygous males include, vascular disease of the heart, brain, peripheral nerves, skin, kidneys, and eyes. Vascular compromise affecting the heart may lead to ischemic heart disease. The central nervous system may be affected leading to seizures, transient ischemic attacks, and ischemic stroke. Peripheral and autonomic neuropathy are common in Fabry disease. Fabry disease patients also develop characteristic ectasia of skin vessels called angiokeratoma. Progressive renal failure is a classic finding in Fabry disease ...
A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated.
Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of crosscorrection (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to ...
Atypical hemolytic-uremic syndrome (aHUS) is a rare, potentially lethal systemic disorder, capable of affecting both adults and children, causing thrombotic microangiopathy (TMA) that leads to the formation of thrombus within small blood vessels with multiple organ failure. The pathogenesis of the aHUS is part of a sort of chronic and uncontrolled activation of the complement system by genetic mutation of some proteins usually responsible for its self-regulation. Today, the rapid diagnosis of the disease and the timely start of treatment with eculizumab, improve outcomes of renal failure, stroke and heart attack. Fabry disease is a rare tesaurismosis, X linked, due to the deficiency of the lysosomal enzyme alpha-galactosidase A, necessary for the physiological catabolism of glycosphingolipids. Multisystem clinical manifestations lead to a serious degenerative pathology. The diagnostic suspicion based on anamnesis and careful research of the symptoms and then confirmed by the enzymatic dosage of ...
In a press release, John Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, Today is a great day for Amicus and the Fabry community. We are pleased to report that the 12 and 24 month results from Study 011 have met our pre-defined criteria for success in terms of substrate reduction at 12 months, as well as clinical measures of kidney function maintained out to 24 months. We believe these data provide important validation that a small-molecule chaperone can restore the function of a patients own enzyme in patients with amenable mutations, and that our pharmacogenomic assays can identify these patients. Together these results demonstrate the power of personalized medicine in rare diseases and offer the prospect of a new treatment option that differs from traditional enzyme replacement therapy. Pending positive data from our second Phase 3 study we expect to meet with regulatory authorities to discuss these data and determine the fastest registration pathway for ...
The concept of enzyme replacement therapy for lysosomal storage diseases was enunciated by de Duve in 1964. However, much cell biology had to be learned before lysosomal enzymes could be developed into pharmaceuticals. A model system, consisting of cultured skin fibroblasts from patients with mucopolysaccharidoses (MPS), showed that their defective glycosaminoglycan catabolism could be corrected by factors derived from cells of a different genotype. The corrective factors were identified as lysosomal enzymes with a special feature, or recognition signal, that would permit efficient uptake. As the recognition signal was absent from a number of lysosomal enzymes secreted by fibroblasts from patients with I-cell disease (a monogenic disorder), it was postulated to be a post-translational modification of the lysosomal enzymes. It was subsequently shown to be a carbohydrate and identified as mannose-6-phosphate (M6P), which was recognized by ubiquitous M6P receptors. A second model system was the clearance,
Presented by Regina Votavová, Lubor Golán, David Zemánek and Aleš Linhart. 2nd Department of Internal Cardiovascular Medicine. First Medical Faculty, Charles University in Prague. General University Hospital in Prague. Czech Republic. Based on the typical distribution of scar tissue as seen on MRI and renal involvement, the patient was suspected of having Anderson Fabry disease (AFD).. Laboratory results confirmed low a-galactosidase A (AGALA) activity in plasma 0.22 (normal range 2.4-11.3 nmol/ml/h) and leukocytes 3.4 (normal values 32.2 - 89.0 nmol/ml/h). The genetic analysis revealed a missense mutation c.902G,A (p.Arg301Gln / p.R301Q).. At present the patient is being considered for mitral valve surgery while having his hepatic lesion and kidney involvement investigated. Renal biopsy is being considered. In the meantime he was started on enzyme replacement therapy (ERT) by agalsidase beta (Fabrazyme ®), 1 mg / kg / every other week.. Anderson - Fabry disease (AFD) (OMIM 301500) is an ...
Semantic Scholar extracted view of Molecular pathology of Fabrys disease. Physical and kinetic properties of alpha-galactosidase A in cultured human endothelial cells. by Douglas L. Johnson et al.
AGAW : Diagnosis of Fabry disease in male patients   Verifying abnormal serum alpha-galactosidase results in male patients with a clinical presentation suggestive of Fabry disease
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Learn about Fabrazyme (Agalsidase Beta) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabrys disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia. For this study, we enrolled 178 patients consecutively admitted to our Neurological Ward for ischemic stroke, transient ischemic attack, intracerebral haemorrhage, neuroradiological evidence of silent infarcts, or white matter lesions possibly related to cerebral vasculopathy at brain MRI, and cerebral venous thrombosis. The qualifying events have to occur between 18 and 55 years of age. We identified two patients with an α-galactosidase A gene variant, with a prevalence of 0.9 %. According to recent diagnostic criteria, one patient, included for the occurrence of multiple white matter lesions at brain MRI, had a diagnosis of definite FD, the other, included for ischemic stroke,
Answers from trusted physicians on symptoms of angiokeratoma fordyce. First: The pathophysiology of angiokeratomas remains unknown, although increased venous pressure may contribute to their formation. Also a case report recommends considering fabry disease in all male patients with angiokeratomas, even if localized to the scrotum.
Amicus Therapeutics: Offering Therapies to Orphan and Rare Diseases. Amicus Therapeutics is an American biopharmaceutical company located in Cranbury, New Jersey. In 2007, Amicus Therapeutic went public under the NASDAQ trading symbol FOLD. Before Amicus went public, several investment capital corporations such as Canaan Partners, New Enterprise Associates, and Radius Ventures funded it.. Amicus Therapeutics focuses on orphan and rare diseases such as Lysosomal Storage Disorder (LSD), genomic connective tissue disorder, Pompe, and Fabry disease. The company is at the pole position of innovative treatments to treat these devastating diseases. The companys primary product, Migalastat, is a modified medicine in its advanced stages of development to treat patients suffering from Fabry disease based on their genomic diagnosis. Another product candidate at its late-stage advancement is the SD-101, which should handle rare genomic connective tissue disorder, Epidermolysis Bullosa (EB). Visit ...
CRANBURY, N.J., June 3, 2015-- Amicus Therapeutics, a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, has submitted a marketing authorization application to request full approval of the oral small molecule pharmacological chaperone Galafold for Fabry patients who have amenable genetic mutations.
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.. Submit only 1 of the following specimens:. Preferred:. Specimen Type: Whole blood. Container/Tube:. Preferred: Lavender top (EDTA) tube or yellow top (ACD) tube. Acceptable: Any anticoagulant. Specimen Volume: 3 mL. Collection Instructions:. 1. Invert several times to mix blood.. 2. Send specimen in original tube.. Specimen Stability Information: Ambient (preferred)/Refrigerated. Acceptable:. Specimen Type: Blood spot. Supplies: Card - Blood Spot Collection (Filter Paper) (T493). Container/Tube:. Preferred: Collection card (Whatman Protein Saver 903 Paper). Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493). Specimen Volume: 2 to 5 Blood spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, ...
The main features of the disease are linked to the deposit of glycolipids (Gb3) in the vascular endothelium, smooth muscle cells, renal epithelium, myocardium, dorsal root ganglia, autonomic nervous system, and the brain. Clinically, it is associated with cerebral strokes, progressive renal failure with proteinuria, cardiac hypertrophy, arrhythmias, valvular insufficiency, and myocardial infarction. Other manifestations of the disease are progressive sensorineural hearing loss, vertigo, postprandial abdominal cramps, and achalasia. Pain is frequent in both hands and feet as a result of progressive neuropathy. Skeletal involvement causes arthralgia, articular erosion, avascular necrosis, and limitation of the temporomandibular joint. As the disease evolves, the lungs become involved and pulmonary function tests confirm the presence of an obstructive ventilator disease. Finally, the characteristic presence of angiokeratomas on the skin, mucous membranes, corneal abnormalities, as well as the ...
AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today an
Amicus Therapeutics shares fell sharply last year on news that management was tossing aside its timeline to file for approval of its Fabry disease therapy Galafold in the United States. However, an application for Galafolds approval was submitted to EU regulators last year, and a decision could come at their next meeting, which is scheduled for March 29 through March 31.. If approved, Galafold will join Shires (NASDAQ:SHPG) Replagel and Sanofis (NYSE:SNY) Fabrazyme as potential treatment options for this disease, which is caused by a missing enzyme. While Replagel and Fabrazyme treat Fabry disease by replacing the missing enzyme, Galafold works differently. In patients who still produce some of the necessary enzyme, Galafold helps those enzymes work more effectively.. Because Galafold has a different mechanism of action than these two other drugs, it could potentially be prescribed in concert with, rather than instead of, them. However, demand for Galafold will be more limited than Replagel ...
A resource for neurologists, neurology residents, medical students on a neurology rotation, and people interested in neurology or neuroscience. Review questions to help you study for the Neurology boards or RITE exam. Helpful PDA medical software.
Subject has been previously treated with Replagal or any other enzyme replacement therapy for Fabry Disease. If the patient has previously been treated with Replagal or another enzyme replacement therapy then they must have been off the therapy for at least 30 days and must have a Day-14 antibody blood sample drawn and that test must be negative for anti-agalsidase alfa IgG and IgE antibodies and not experienced a prior severe infusion reactions with prior enzyme replacement therapy ...
Purchase high purity enzyme alpha-Galactosidase (Aspergillus niger) for use in research, biochemical enzyme assays and in vitro diagnostic analysis.
We report studies of bleaching action in an epitaxial Fabryâ€Perot resonator grown by molecular beam epitaxy. These new structures hold exciting potential for surface-emitting lasers, optical switches, and optical modulators. The structure consisted of a multiple quantum well of AlGaAs and GaAs surrounded by two quarter-wave high reflectors with alternating layers of AlAs and AlGaAs. The spectral and temporal transmittances under intense optical pulses are reported here. The spectral data provide simultaneous information on nonlinear changes in both real and imaginary parts of the refractive index. The temporal data show that the transmittance can be switched up to three orders of magnitude in less than the experimental resolution of 300 ps, and provide evidence for time compression of optical pulses ...
Fever & Nausea & Peripheral Neuropathy & Rheumatic Fever Symptom Checker: Possible causes include Fabry Disease. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Electrolyte Imbalance & Tinnitus Symptom Checker: Possible causes include Fabry Disease. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
★★★ Tinnitus And Craniosacral Therapy Diy Causes Of Transient Pulsatile Tinnitus Tinnitus At 27 Fabry Disease Corneal Opacity Tinnitus This Protein Cured 105…
Massart A, Pallier A, Pascual J, Viklicky O, Budde K, Spasovski G, Klinger M, Sever MS, Sørensen SS, Hadaya K, Oberbauer R, Dudley C, De Fijter JW, Yussim A, Hazzan M, Wekerle T, Berglund D, De Biase C, Pérez-Sáez MJ, Mühlfeld A, Orlando G, Clemente K, Lai Q, Pisani F, Kandus A, Baas M, Bemelman F, Ponikvar JB, Mazouz H, Stratta P, Subra JF, Villemain F, Hoitsma A, Braun L, Cantarell MC, Colak H, Courtney A, Frasca GM, Howse M, Naesens M, Reischig T, Serón D, Seyahi N, Tugmen C, Alonso Hernandez A, Beňa L, Biancone L, Cuna V, Díaz-Corte C, Dufay A, Gaasbeek A, Garnier A, Gatault P, Gentil Govantes MA, Glowacki F, Gross O, Hurault de Ligny B, Huynh-Do U, Janbon B, Jiménez Del Cerro LA, Keller F, La Manna G, Lauzurica R, Le Monies De Sagazan H, Thaiss F, Legendre C, Martin S, Moal MC, Noël C, Pillebout E, Piredda GB, Puga AR, Sulowicz W, Tuglular S, Prokopova M, Chesneau M, Le Moine A, Guérif P, Soulillou JP, Abramowicz M, Giral M, Racapé J, Maggiore U, Brouard S, Abramowicz D. The ...
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University of Texas MD describes symptoms, treatment, and prognosis for patients suffering with this rare but severe lysosomal disorder. ...
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Mierke, C. T. , Kollmannsberger, P. , Zitterbart, D. , Diez, G. , Koch, T. M. , Marg, S. , Ziegler, W. H. , Goldmann, W. H. and Fabry, B. (2010 ...
FAGPL : Draw blood in a plain red-top tube(s), serum gel tube(s) is acceptable. Spin down and send 2 mL of serum refrigerated in a plastic vial.