Biomarkers for Diagnosing and Staging of Fabry Disease

2018 ◽  
Vol 25 (13) ◽  
pp. 1530-1537 ◽  
Author(s):  
Johannes Kramer ◽  
Frank Weidemann
Keyword(s):  
Fabry Disease ◽  
Clinical Relevance ◽  
Cardiac Involvement ◽  
Lysosomal Storage ◽  
Timely Initiation ◽  
Disease Biomarkers ◽  
Long Time ◽  
New Biomarkers ◽  
Deficient Activity

Background: Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α -galactosidase A which leads to progressive intracellular accumulation of globotriaosylceramide in tissues and organs including heart, kidney, vascular endothelium, the nervous system, the eyes and the skin. Cardiac involvement is common, leads to fatal complications and is mainly responsible for reduced life expectancy in Fabry disease. The exact staging of disease progression and timely initiation of treatment is essential in Fabry disease. Therefore, it is essential to use the possibilities of specific biomarkers for early detection of organ involvement or early diagnosis. Methods: By the use of Pubmed all relevant papers for biomarkers in Fabry disease were screened. The quality of retrieved papers was appraised using standard tools. Finally, 70 peer reviewed paper were included. Results: In the past biomarkers for Fabry disease biomarkers did not have clinical relevance. Nowadays, a lot of research is focusing on identification of new biomarkers and their clinical relevance. Only two biomarkers reached clinical applicability. Lyso-GB3 for identification of atypical FD variants and hsTNT for identification of cardiac involvement, which should indicate further diagnostics. Treatment response to ERT can be monitored by lyso-GB3 but data for long-time outcome are missing. A lot of GB3-related analogs are identified in urine and plasma, some of which might play an important role for managing Fabry disease in future. Conclusion: In conclusion, we suggest to measure lyso-GB3 and hsTNT at least once a year. The routine measurement of these two biomarkers will help now for the staging of every individual patient and in addition, will help for a better general understanding of Fabry disease.

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

2015 ◽  
Author(s):  
Stephen Waldek
Keyword(s):  
Fabry Disease ◽  
Ventricular Hypertrophy ◽  
Severe Disease ◽  
Sensorineural Deafness ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Long Time ◽  
Alpha Galactosidase ◽  
Multiorgan Disease ◽  
Echocardiographic Evidence

Fabry disease is a rare X-linked lysosomal storage disorder in which deficiency of alpha-galactosidase A leads to accumulation of substrate, mostly globotriaosylceramide, which causes a progressive, multiorgan disease affecting predominantly the kidneys, skin, heart, gut, and nervous system. Painful peripheral (‘acral’) neuropathy is characteristic. The disease is commonly diagnosed in children and young men often after some years of usually neuropathic symptoms, with exacerbations (Fabry crises), that commonly elude diagnosis for a long time. These usually occur years in advance of overt involvement of other organs. Diagnosis may also be suspected from renal biopsy, echocardiographic evidence of cardiomyopathy commonly beginning as left ventricular hypertrophy, or characteristic angiokeratomas typically in ‘bathing trunk’ distribution on skin. Renal manifestations are of proteinuria leading to progressive chronic kidney disease associated with deposits in podocytes. Diarrhoea is common. Disordered sweating is typical. Corneal lesions are also typical and there may be tortuosity of retinal vessels. Strokes are increased in frequency, and sensorineural deafness may occur. Women have fewer and later overt manifestations but some develop severe disease.

scholarly journals Migalastat Treatment in a Kidney-Transplanted Patient with Fabry Disease and N215S Mutation: The First Case Report

2021 ◽  
Vol 14 (12) ◽  
pp. 1304
Author(s):  
Valeria Di Stefano ◽  
Marta Mancarella ◽  
Antonia Camporeale ◽  
Anna Regalia ◽  
Marta Ferraresi ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cardiac Involvement ◽  
Late Onset ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Fabry Patient ◽  
First Case ◽  
Gla Gene ◽  
Stage Renal Disease ◽  
End Stage

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-galactosidase A activity and, consequently, to glycosphingolipid accumulation in a wide variety of cells. Fabry disease due to N215S (c.644A>G, p.Asn215Ser) missense mutation usually results in a late-onset phenotype presenting with isolated cardiac involvement. We herein present the case of a patient with N215S mutation with cardiac involvement, namely left ventricular hypertrophy and ventricular arrhythmias, and end-stage renal disease requiring kidney transplantation. To the best of our knowledge, this is the first report of a kidney-transplanted Fabry patient treated with oral pharmacologic chaperone migalastat.

scholarly journals A Case of a 50-Year-Old Woman with Typical Fabry Disease Who Showed Serial Electrocardiographic and Echocardiographic Changes over a 17-Year Period

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Su Nam Lee ◽  
Gee-Hee Kim ◽  
Ki-Dong Yoo
Keyword(s):  
Fabry Disease ◽  
Ventricular Hypertrophy ◽  
Cardiac Involvement ◽  
Premature Death ◽  
Vascular Wall ◽  
Lag Time ◽  
Left Ventricular ◽  
The Body ◽  
Lysosomal Storage ◽  
Major Organ

Fabry disease (FD) is a progressive, X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A activity. Affected individuals accumulate globotriaosylceramide and glycosphingolipids in the lysosomes and cytoplasm of cells throughout the body, leading to major organ failure and premature death. Cardiac involvement includes left ventricular hypertrophy, arrhythmia, endothelial dysfunction at vascular wall, and cardiomyopathy. The diagnosis of FD can be difficult and there is often a long lag time between symptoms and diagnosis. Here, we present a case of a 50-year-old woman with typical Fabry disease who showed serial electrocardiographic and echocardiographic changes over 17 years prior to diagnosis with Fabry disease.

scholarly journals Psychiatric Treatment Process of an Elderly Woman Patient Diagnosed with Anderson-Fabry Disease

2021 ◽  
Author(s):  
Mehmet Hamdi Orum
Keyword(s):  
Fabry Disease ◽  
Vascular Endothelium ◽  
Treatment Process ◽  
Storage Disease ◽  
Psychiatric Treatment ◽  
Psychiatric Symptoms ◽  
Behavioral Therapy ◽  
Treatment Compliance ◽  
Lysosomal Storage

Anderson-Fabry disease (AFD) is a lysosomal storage disease characterized by accumulation of glycosphingolipids in all tissues and especially in the vascular endothelium. Kidney, heart, skin and eye are often affected organs. The nervous system and brain may also be affected primarily or secondary, and AFD may present with psychiatric symptoms. Herein, we discussed a female patient with AFD who had severe psychiatric symptoms. The patient was managed by cognitive behavioral therapy plus psychotropic medications. The early detection of psychiatric disorders in patients with AFD may improve the quality of life and may increase treatment compliance.

scholarly journals P1832 T1 mapping and echo-global longitudinal strain are early markers of cardiac involvement in patients with fabry disease

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
C Gatterer ◽  
D Beitzke ◽  
P E Bartko ◽  
M Schneider ◽  
T Binder ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Longitudinal Strain ◽  
T1 Mapping ◽  
Cardiac Involvement ◽  
Global Longitudinal Strain ◽  
Lysosomal Storage Diseases ◽  
Left Ventricular ◽  
Study Cohort ◽  
Lysosomal Storage ◽  
Enzyme Replacement

Abstract OnBehalf Constantin Gatterer Introduction Fabry disease (FD) is one of the most common lysosomal storage diseases caused by deficiency of Alpha-Galactosidase A and accumulation of glycosphingolipids in all cells containing lysosomes. Cardiac involvement is characterized by left ventricular hypertrophy, conduction abnormalities and myocardial fibrosis with consecutive cardiomyopathy in late stages. Purpose As the detection of early signs of cardiac involvement is crucial for the initiation of enzyme replacement therapy (ERT) or Chaperon therapy, we intended to find early imaging markers. Methods Cardiac MRI (CMR) including Late Gadolinium Enhancement (LGE), representing fibrosis, and T1-mapping as well as echocardiography with measurement of global longitudinal strain (GLS) were done as part of the regular check-ups for patients with FD. Results The study cohort of 30 FD patients (20-69 years, 53% women) in different stages of disease showed low GLS values already at the time of baseline echocardiography (mean: -17,22%), correlating with the amount of LGE (r = 0,73; p = 0,003) and ejection fraction measured by CMR (CMR-EF; r=-0,74; p = 0,002). After an average follow-up of 39 months (STD 18), GLS values were significantly declined (-15,51 %; p = 0,009) and correlated with T1 times (r = 0,7; p = 0,04), while LGE and CMR-EF did not significantly change compared to baseline. Baseline T1 times correlated negatively with the reduction of GLS (r=-0,7; p = 0,003), while LGE and CMR-EF showed no correlation with the course of GLS. ERT appeared to have no influence on the extend of GLS reduction. Conclusion Low native CMR T1 times, indicating sphingolipid accumulation in the myocardium, seem to represent the beginning of cardiac involvement in FD and might predict the course of GLS. GLS is a sensitive parameter for early detection of cardiac manifestation and disease progression, while LGE and CMR-EF could not recognize slight deterioration of left ventricular function.

scholarly journals Survey about the Quality of Life of Italian Patients with Fabry Disease

Diseases ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 72
Author(s):  
Barbara Polistena ◽  
Donato Rigante ◽  
Ludovico Luca Sicignano ◽  
Elena Verrecchia ◽  
Raffaele Manna ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Fabry Disease ◽  
Descriptive Analysis ◽  
Central Italy ◽  
Well Being ◽  
Computer Assisted ◽  
Lysosomal Storage ◽  
Related Quality ◽  
Health Related

Fabry disease (FD) is a genetic disease included in the group of lysosomal storage disorders, caused by X-linked deficiency of the enzyme alpha-galactosidase A. The aim of this study was to evaluate different aspects related to the quality of life (QoL) of a multicentre cohort of Italian patients with FD. An observational survey was conducted to measure health-related quality of life (HR-QoL) in FD patients using the CAPI (Computer-Assisted Personal Interview) method: 106 patients (mostly women) responded to the questionnaire. Geographically, 53.7% of patients lived in northern Italy, 18.9% in central Italy and 27.4% in southern Italy or the Islands. All data were collected through a five-dimensional EuroQoL questionnaire referring to functional aspects (mobility, personal care, routine activities) and perception of physical/mental well-being (pain or discomfort, anxiety or depression). A descriptive analysis of responses was performed; FD patients were compared in terms of QoL with subjects suffering from other chronic diseases, such as Crohn’s disease, chronic hepatitis, cirrhosis and multiple sclerosis. Difficulty in normal daily activities was reported by 47.2% of FD patients. About one third of subjects also had mobility difficulties. Feelings of loneliness and isolation were reported by 33.3% of those being 60–69 years old. Anxiety was equally reported in both oldest and youngest patients (66.7%), while depression, relational problems, fear of other people’s judgement increased along with age, reaching 66.7% in the over-70-years group. Male patients were largely troubled about the risk of physical disability, particularly those aged 60 years or over. Furthermore, FD patients had a poorer QoL than people suffering from other chronic inflammatory disorders. Our study upholds that FD patients have a poor QoL, as already known, negatively impacting psychic well-being and social activities. Our survey has also found a worse QoL in FD patients compared with other severe chronic disorders.

Tingkat Pemahaman Kompetensi Guru Pada Mahasiswa Pendidikan Geografi Sebagai Calon Guru Geografi

2020 ◽  
Vol 21 (1) ◽  
pp. 102-117
Author(s):  
Novia Zalmita ◽  
Muhajirah Muhajirah ◽  
Abdul Wahab Abdi
Keyword(s):  
Prospective Teachers ◽  
Prospective Teacher ◽  
Quantitative Description ◽  
Population Data ◽  
Geography Education ◽  
Teacher Competence ◽  
Education Department ◽  
Long Time

One that influences human resource indicators is education. The teacher is a profession as a job of academic specialization in a relatively long time in college. Understanding related to teacher competence is very important to have by a prospective teacher because it can affect the quality of performance as a professional teacher. The teacher's competence is known as pedagogic, professional, social and personality competencies. The issue in this study is how the competency of the teacher of the Department of Geography Education FKIP Unsyiah as a prospective teacher of geography? The purpose of this study was to determine the competence of teachers in the Department of Geography Education FKIP Unsyiah as prospective geography teachers. Quantitative description approach is used in this study to find answers to the issue. The population in this study were students of the Department of Geography Education FKIP Unsyiah class of 2015 and 2016 who had been declared to have passed the Micro Teaching and Magang Kependidikan 3 course totaling 50 people. Because the population is small and can be reached, the determination of the sample using total sampling techniques so that the sample in this study is the whole population. Data collection is done by distributing test questions to respondents. The data was analyzed using the descriptive statistics percentage formula. The results of the study indicate that the level of teacher competence of Geography Education Department students as prospective teachers is in the moderate category, namely as many as 22 respondents (44%). A total of 12 respondents (24%) were in the high category, 15 respondents (30%) were in the low category and 1 respondent (2%) were in the very low category.

Electrical Damage Due to Low Energy Plasma Processing of GaAs Structures

1991 ◽  
Vol 223 ◽  
Author(s):  
Hans P. Zappe ◽  
Gudrun Kaufel
Keyword(s):  
Chemical Processes ◽  
Low Energy ◽  
Electrical Behavior ◽  
Rapid Thermal Anneal ◽  
High Temperature Anneal ◽  
Significant Damage ◽  
Low Energies ◽  
Long Time ◽  
Physical Plasma

ABSTRACTThe effect of numerous plasma reative ion etch and physical milling processes on the electrical behavior of GaAs bulk substrates has been investigated by means of electric microwave absorption. It was seen that plasma treatments at quite low energies may significantly affect the electrical quality of the etched semiconductor. Predominantly physical plasma etchants (Ar) were seen to create significant damage at very low energies. Chemical processes (involving Cl or F), while somewhat less pernicious, also gave rise to electrical substrate damage, the effect greater for hydrogenic ambients. Whereas rapid thermal anneal treatments tend to worsen the electrical integrity, some substrates respond positively to long-time high temperature anneal steps.

PEMBENAHAN TERHADAP LEMBAGA PEMASYARAKATAN DAPAT MENIADAKAN OPSI HUKUMAN MATI BAGI NARAPIDANA DI INDONESIA (THE IMPROVEMENT OF QUALITY OF PENITENTIARY CAN ELIMINATE THE DEATH PENALTY OPTIONS OF CONVICTED CRIMINALS IN INDONESIA)

2020 ◽  
Vol 10 (2) ◽  
pp. 175
Author(s):  
Nomensen Freddy Siahaan
Keyword(s):  
Death Penalty ◽  
Deterrent Effect ◽  
Criminal Cases ◽  
Psychological Burden ◽  
The Real ◽  
The Public ◽  
Good Citizen ◽  
The People ◽  
Long Time

After a long time was not heard to the public area, lately death penalty toward the criminal cases that classified as extraordinary crime are appear. The author discovers electronic article about the execution of the death penalty which is the prosecutor prepares to execute death penalty toward the drugs dealer. The president of Republic of Indonesia stated that it is necessary to give a deterrent effect to the convicted  criminal and keep the morality of Indonesian teenagers. According to my opinion, the author argues that it will be better and wiser if we discuss about renovating all of the Penitentiary in Indonesia than debating whether death penalty could be done in Indonesia or not, because it will be displeasure many parties, death penalty infringed the human rights of the convicted criminals and cause psychological burden to them, families, the executor of the death penalty, and other parties. Because if we have to improve the quality of the Penitentiary, if the function of Penitentiary for fostering moralily has been optimal or properly enough to the convicted criminals, Indonesia will be no longer need the death penalty option as sanction to the convicted crimanals including for the extraordinary crime (especially for drugs trafficking in our country). Penitentiary is one of the public services which aims for fostering the people that initially have bad habits (commited to the crime), so that they will have the awareness to change their bad attitude into the be better ones, will not harm others, and positively contributed to the society. Already Penitentiary’s conditions should be designed in such a way and as good as possible, so that the inmates feels like at their own home (like having a second home after his own home), and feel humaner to spend their days in the Penitentiary. The author believes that if the Penitentiary has been improved and optimized its function well, then the real purpose of Penitentiary will definitely achieved. As stated in Law Number 12 Year 1995 regarding to Penitentiary Article 2 which states "sanction system are organized in order to fostering the convicted criminals in order to be the real man, aware of their fault, improve themselves, and not to repeat the criminal act so that they can be friendly received by the community, can actively participated in the development of our country, and can socialize themselves as good citizen."Article 3 on this regulation also intensifies the function of Penitentiary "the function of Penitentiary is to prepare convicted criminals to be able to properly integrated to the society, so they can be accepted again as members of the public who are free and responsible ones." 

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