scholarly journals ANDERSON-FABRY DISEASE: MANIFESTATION AND PROGNOSIS

2017 ◽  
pp. 46-50
Author(s):  
N. O. Pichkur
Keyword(s):  
Fabry Disease ◽  
Activity Level ◽  
Social Adaptation ◽  
Disease Manifestation ◽  
Enzyme Replacement ◽  
Renal Manifestation ◽  
Patient State ◽  
Alpha Galactosidase ◽  
Stage Renal Disease ◽  
End Stage

The aim of the study was to describe diagnostic and treatment experience of Fabry disease in Ukraine, rare inherited multisystem metaboliс disorder with chronic kidney insufficiency as one of signs. The diagnosis was found in nine years old boy with acroparestesia and multiply angiokeratomas after enzymodiagnostic test (determination of lysosomal enzyme alpha-galactosidase A activity level in peripheral blood leucocytes). The parents gave consent to examine of the other child in family, 19 years old boy with myeloradiculonevritis and inferior paraparesis, and glomerulonephritis presented by proteinuria. Fabry disease was confirmed in proband by special enzymodiagnostic test. Clinical-genealogical analysis was exposed by the "phenomenon of grandfather": grandfather exitus from End Stage Renal Disease, probably due renal manifestation of Fabry disease. Enzyme replacement therapy was stabilized patient state, decreased the proteinuria level and saved the renal function. Early and classic signs of Fabry disease which allows to suspect a genetic anomaly were presented in article. Information about Fabry disease physician followed by in-time diagnosis and onset of specific therapy those provide favorable disease course, social adaptation and rehabilitation of patient, effective medical-genetic consultation in gen-compromised families.

P0081IMPACT OF RENAL FAILURE ON OVERALL SURVIVAL OF PATIENTS WITH FABRY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ekaterina Karovaikina ◽  
Sergey Moiseev ◽  
Nikolay Bulanov ◽  
Alexey Moiseev ◽  
Agunda Kuchieva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Failure ◽  
Fabry Disease ◽  
Survival Function ◽  
Chronic Hemodialysis ◽  
Dialysis Initiation ◽  
Rank Test ◽  
Enzyme Replacement ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims End-stage renal disease (ESRD) is associated with significant morbidity and mortality among patients with Fabry disease (FD). The aim of our study was to evaluate impact of renal failure on overall survival of patients with FD. Method We recruited 117 adult (>18 years) patients with FD that was confirmed by enzymatic and genetic studies. ESRD was defined according to the KDIGO guidelines (2012). Kaplan-Meyer analysis and Log Rank test were used to estimate overall survival of patients with FD. Results Thirty-seven (36 males and 1 female) of 117 patients had ESRD. Thirty-three of them were treated with chronic hemodialysis, whereas four patients have undergone renal transplantation. Among patients with ESRD eleven (29.7%) patients died at the median age of 43 (37; 46) years. All deceased patients were males. The median time from dialysis initiation to death was 32 (6; 67) months. The causes of death included sudden cardiac death (n=9), stroke (n=1) and peritonitis (n=1). Only 2 deceased patients received enzyme replacement therapy over 3 and 11 months. There were deaths only in the ESRD group (Table). There was a decline in survival function after the age of 30 years in patients with ESRD. In Kaplan-Meyer analysis overall survival was 51.2 years (95% Confidence interval 47.7-54.7) and was lower in patients with ESRD (Log Rank (mantel-Cox) χ2=17.5, df 1, р<0.0001, Figure). Five- and 10-year survival after dialysis initiation was 72.5% and 54.1%, respectively. Conclusion ESRD was the major factor associated with low survival of patients with FD in Russia. One out of every 3 dialysis patients died in 5 years after dialysis initiation.

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.

La diagnosi precoce di malattia

2019 ◽  
Vol 31 (1) ◽  
pp. 58-60
Author(s):  
Federica Rossi ◽  
Federico Pieruzzi
Keyword(s):  
Wide Spectrum ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
The Body ◽  
Lysosomal Storage ◽  
Cerebrovascular Complications ◽  
Risk Patients ◽  
Alpha Galactosidase ◽  
Stage Renal Disease ◽  
End Stage

Anderson-Fabry disease is an X-linked, lysosomal, storage disorder characterized by the decreased activity of alpha-Galactosidase A, which results in accumulation of globotriaosylceramide (Gb-3) in cells and tissues throughout the body, leading to a wide spectrum of clinical manifestations. Patients are often misdiagnosed or diagnosed late in their life. This is due to the phenotypic heterogeneity, the poor awareness of this rare disease, and many pitfalls when making a differential diagnosis, in adulthood, as well as in the early stages. Delayed diagnosis has significant clinical implications, because the progression of the disease over time can lead to irreversible end-stage renal disease and life-threatening cardiovascular or cerebrovascular complications. Early diagnosis remains essential in order to start an early treatment and reduce the progression of the disease, thus maximizing the chance to improve patient outcomes. Newborn screening, high-risk patients’ identification, and increasing pediatricians’ and clinicians’ knowledge on this condition, are good strategies to avoid late referrals of Anderson-Fabry patients to reference centers.

scholarly journals Circulating microRNAs in Fabry Disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ke Xiao ◽  
Dongchao Lu ◽  
Jeannine Hoepfner ◽  
Laura Santer ◽  
Shashi Gupta ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Premature Death ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Significant Differential Expression ◽  
Enzyme Replacement ◽  
Beneficial Effects ◽  
Mirna Sequencing ◽  
Continuous Progress ◽  
Alpha Galactosidase

Abstract Fabry disease is an X-linked deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal). This results in an accumulation of globotriaosylceramide (GL-3/Gb3) in a variety of cells with subsequent functional impairment. The continuous progress of FD often leads to decreased quality of life and premature death caused by multi-organic complications. The overall aim of our study was to determine the amount of circulating miRNAs in Fabry patients and to test whether ERT would alter the level of individual circulating miRNAs. We used miRNA sequencing by the HTG EdgeSeq System to identify the circulating miRNA pool from Fabry patients with and without enzyme replacement therapy (n = 6). In total, 296 miRNAs in serum of patients were identified. Among them 9 miRNAs were further evaluated in extra serum samples (n = 31) using real-time qPCR and 6 of them showed significant differential expression. The resulting miRNA pattern may help to better understand mechanisms involved in the beneficial effects of ERT and these new miRNA markers could help to estimate the efficacy of ERT or to identify Fabry patients with specific need for ERT.

scholarly journals Cell Transplantation Combined with Recombinant Collagen Peptides for the Treatment of Fabry Disease

2020 ◽  
Vol 29 ◽  
pp. 096368972097636
Author(s):  
Daisuke Kami ◽  
Masashi Yamanami ◽  
Takahiro Tsukimura ◽  
Hideki Maeda ◽  
Tadayasu Togawa ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cell Transplantation ◽  
Financial Burden ◽  
Kidney Injury ◽  
The Body ◽  
Term Survival ◽  
Enzyme Replacement ◽  
Continuous Release ◽  
Alpha Galactosidase

Fabry disease is caused by a decrease in or loss of the activity of alpha-galactosidase, which causes its substrates globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to accumulate in cells throughout the body. This accumulation results in progressive kidney injury due to glomerulosclerosis and in heart failure due to hypertrophy. Enzyme replacement therapy (ERT) has been used as the standard therapy for Fabry disease, but it causes a significant financial burden, and regular administration is inconvenient for patients. Because of the short half-life of alpha-galactosidase in vivo, therapeutic methods that can supplement or replace ERT are expected to involve continuous release of alpha-galactosidase, even at low doses. Cell transplantation therapy is one of these methods; however, its use has been hindered by the short-term survival of transplanted cells. CellSaic technology, which utilizes cell spheroids that form after cells are seeded simultaneously with a recombinant collagen peptide scaffold called a μ-piece, has been used to improve cell survival upon implantation. In this study, syngeneic murine embryonic fibroblasts were used to generate CellSaic that were transplanted into Fabry mice. These spheroids survived for 28 days in the renal subcapsular space with forming blood vessels. These results indicate CellSaic technology could be a platform to promote cellular graft survival and may facilitate the development of cell transplantation methods for lysosomal diseases.

Diagnosis of Fabry disease in a patient with end stage renal disease on hemodialysis: A case report

2018 ◽  
Vol 123 (2) ◽  
pp. S77-S78
Author(s):  
Jin Sug Kim ◽  
Yu Ho Lee ◽  
Su Woong Jung ◽  
Kyung Hwan Jeong ◽  
Tae Won Lee ◽  
...  
Keyword(s):  
Case Report ◽  
Renal Disease ◽  
Fabry Disease ◽  
End Stage Renal Disease ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease in older people

2013 ◽  
Vol 23 (3) ◽  
pp. 177-188 ◽  
Author(s):  
AH Abdelhafiz ◽  
C Bailey ◽  
J Russell ◽  
M El Nahas
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Older People ◽  
Disease Prevalence ◽  
Geriatric Syndromes ◽  
Very Elderly ◽  
Renal Manifestation ◽  
Chronic Kidney Disease Prevalence ◽  
Stage Renal Disease ◽  
End Stage

SummaryChronic kidney disease prevalence will continue to rise due to increased life expectancy and population ageing. It is likely that the decline in glomerular filtration rate with increasing age represents a renal manifestation of widespread vascular disease. In addition to its associated cardiovascular risk, chronic kidney disease in older people is associated with increased prevalence of geriatric syndromes such as functional and cognitive decline, which lead to disability and frailty. Competing risks for mortality, because of the co-existence of multiple co-morbidities in old age, means that the majority of older people with chronic kidney disease will not progress to end-stage renal disease. Management of chronic kidney disease in older people is complex and an individualized and holistic, rather than disease-orientated, approach is necessary, which takes into account patients’ priorities and wishes, especially frail and very elderly populations with multiple co-morbidities.

Conjunctival lymphangiectasia associated with classic Fabry disease

2017 ◽  
Vol 102 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Melanie D Sivley ◽  
Eric L Wallace ◽  
David G Warnock ◽  
William J Benjamin
Keyword(s):  
Fabry Disease ◽  
Dry Eye ◽  
Imaging System ◽  
University Of Alabama ◽  
Multisystem Disease ◽  
Enzyme Replacement ◽  
Clinical Presentations ◽  
Alpha Galactosidase ◽  
The University

BackgroundFabry disease (FD) is a treatable multisystem disease caused by a defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal verticillata, are among the earliest diagnostic findings. Conjunctival lymphangiectasia (CL) has not previously been associated with FD.MethodsWe examined the eyes of a cohort of 13 adult patients, eight men and five women, with documented classic FD, all treated with enzyme replacement therapy (ERT) at the University of Alabama at Birmingham between February 2014 and April 2015. The average age was 48 years with a range of 35–55 years for men and 21–71 years for women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years) with a range of 4–14 years. Classical Fabry mutations included Q283X, R227X, W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap imaging system was used to record conjunctival images.ResultsCL was observed in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations included single cysts, beaded dilatations and areas of conjunctival oedema. Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects (77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were symptomatic, and 10 had peripheral lymphoedema.ConclusionCL represents a common but under-recognised ocular manifestation of FD, which persists despite ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.

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