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 Family genetic screening in rare hereditary diseases

2021 ◽  
Vol 31 (4) ◽  
pp. 6-12
Author(s):  
S.I. Kutsev ◽  
S. Moiseev
Keyword(s):  
Fabry Disease ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Hereditary Diseases ◽  
Lysosomal Storage ◽  
Family Screening ◽  
At Risk Populations ◽  
Ischemic Attack ◽  
Stage Renal Disease ◽  
End Stage

Family genetic testing of probands with newly diagnosed rare hereditary diseases including Fabry disease improves early diagnosis and allows to initiate specific treatment, if available, at earlier stage in affected family members. Diagnosis of Fabry disease, an X-linked lysosomal storage disorder affecting kidneys, heart, brain and other organs, is usually late due to low awareness of physicians about rare diseases. Moreover, early symptoms can be non-specific (e.g. gastrointestinal disorders and autonomic neuropathy) or misleading (e.g. recurrent unexplained fever) whereas characteristic skin rash and keratopathy (cornea verticillata) are frequently overlooked. Undiagnosed patients with Fabry disease can be detected by screening in at-risk populations, such as patients with end-stage renal disease undergoing dialysis or renal transplantation, patients with unexplained left ventricular hypertrophy, and young adults with a history of stroke or transient ischemic attack who have a higher prevalence of the disease compared to general population. High-risk screening paves the way to family screening to identify affected relatives, including children, who can benefit from earlier treatment and genetic counselling. The major barriers to family screening include costs of testing, cultural and societal issues, stigma associated with a diagnosis of genetic disease, low contacts in the family, weak infrastructure, national regulations.

First case of late onset cardiac phenotype Fabry disease due to an AluYb8 insertion in exon 7 of the GLA gene

2019 ◽  
Vol 20 (10) ◽  
pp. 1182-1182
Author(s):  
Constantin Gatterer ◽  
Dietrich Beitzke ◽  
Raute Sunder-Plassmann ◽  
Gere Sunder-Plassmann ◽  
Senta Graf
Keyword(s):  
Fabry Disease ◽  
Late Onset ◽  
Cardiac Phenotype ◽  
First Case ◽  
Gla Gene

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease

Cardiology ◽  
2019 ◽  
Vol 144 (3-4) ◽  
pp. 125-130 ◽  
Author(s):  
Daniela Marisa Carvalho Silva ◽  
Nuno Marques ◽  
Olga Azevedo ◽  
Gabriel Miltenberger-Miltenyi ◽  
Dina Bento ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Fabry Disease ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Gene Variants ◽  
Fabry Patient ◽  
Enzyme Replacement ◽  
Disease Awareness ◽  
Classic Phenotype ◽  
Gla Gene

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

Rare presentation of Fabry disease as ‘burnt-out’ hypertrophic cardiomyopathy

2021 ◽  
Vol 14 (9) ◽  
pp. e243604
Author(s):  
Sam Williams ◽  
Ahmed El-Medany ◽  
Angus Nightingale ◽  
Yasmin Ismail
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Fabry Disease ◽  
Left Ventricular ◽  
Diagnostic Tools ◽  
Lysosomal Storage ◽  
Rare Presentation ◽  
Enzyme Replacement ◽  
End Stage Heart Failure ◽  
End Stage

We herein report the case of a 53-year-old man who was historically diagnosed with hypertrophic cardiomyopathy (HCM) and was lost to follow-up, before presenting with end-stage heart failure. This was initially suspected as dilated cardiomyopathy and then ‘burnt-out phase’ of HCM but subsequently the underlying diagnosis was Fabry disease. Fabry disease is an uncommon lysosomal-storage disease due to reduced or absent activity of the alpha-galactosidase A enzyme. Cardiac involvement most frequently comprises left ventricular hypertrophy. Early treatment of the underlying condition with enzyme replacement therapy may prevent the progression to end-stage heart failure. Fabry disease should be considered in all patients presenting with a clinical phenotype of HCM and a historical diagnosis should be re-evaluated in light of new diagnostic tools. Untreated Fabry can progress to a ‘burnt out’ phase, whereby initial hypertrophy undergoes eccentric remodelling to a dilated, severely impaired left ventricle.

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 Genotype–Phenotype Correlation in a New Fabry-Disease-Causing Mutation

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 122
Author(s):  
Agnė Čerkauskaitė ◽  
Rimantė Čerkauskienė ◽  
Marius Miglinas ◽  
Arvydas Laurinavičius ◽  
Can Ding ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Novel Mutation ◽  
Brain Magnetic Resonance Imaging ◽  
Left Ventricular ◽  
Lysosomal Storage ◽  
Exon 2 ◽  
Progressive Dyspnea ◽  
Reduced Physical Activity ◽  
Magnetic Resonance Imaging Mri ◽  
Gla Gene

Background: Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by α-galactosidase A deficiency leading to intracellular glycosphingolipid accumulation. FD manifestation is multisystem, and can differ depending on disease-related genetic variants. Currently, more than 700 different FD-causing mutations have been identified in the human GLA gene. We identified a novel mutation in a Lithuanian family with classical manifestations of Fabry disease, revealing severe effects to the cardiovascular systems of heterozygous women. Case presentation: A 49-year-old woman underwent echocardiography due to progressive dyspnea that lasted seven years, reduced physical activity, and periodic cardiac arrhythmia. Echocardiography revealed left ventricular hypertrophy with normal diastolic function. The patient had experienced acroparesthesia in her upper limbs and abdominal pain since childhood, and in the last decade had experienced mild proteinuria without renal failure. Her renal biopsy was typical for Fabry disease. The patient’s brain magnetic resonance imaging (MRI) (T2 flair) showed white matter hyperintensities lesions. DNA sequencing of the proband, her mother and one of her sons showed a novel GLA gene exon 2 mutation, c.270C>G (p.Cys90Trp). All three patients had decreased α-galactosidase A activity and specific FD manifestations. Conclusions: A novel GLA mutation, c.270C>G (p.Cys90Trp), was found in a Lithuanian family with a classical form of Fabry disease in heterozygous women with predominant cardiac involvement. However, the exact manifestation of this mutation is still unclear as it is newly reported and further research must be done.

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.

Nephropathic Cystinosis in Adults

2016 ◽  
Author(s):  
Aude Servais
Keyword(s):  
Age Of Onset ◽  
Late Onset ◽  
First Year ◽  
Nephropathic Cystinosis ◽  
Lysosomal Storage ◽  
Crystal Deposition ◽  
Proximal Tubulopathy ◽  
Stage Renal Disease ◽  
End Stage ◽  
First Year Of Life

Cystinosis is an autosomal recessive lysosomal storage disorder caused by a defect in the carrier-mediated system that normally transports cystine out of lysosomes. As a consequence, tissues accumulate variable amounts of the disulphide amino acid cystine. Three overlapping clinical phenotypes are recognized, varying in severity and age of onset. The most severe, the infantile nephropathic form (MIM 219800), appears in the first year of life. The late-onset form (MIM 219900) is also nephropathic, while ocular, non-nephropathic cystinosis manifests largely with corneal crystal deposition (MIM 219750). Infantile cystinosis is the most common form. Affected children develop renal proximal tubulopathy at 6 to 12 months of age. In the absence of treatment, renal failure occurs, with progression to end-stage renal disease (ESRD). Cystine crystal deposition in the cornea leads to photophobia and continuous widespread cystine accumulation eventually leads to rickets, retinal, endocrinological (hypothyroidism and impaired glucose tolerance), hepatic, gastrointestinal, muscular, and neurological abnormalities.

scholarly journals Deficiency in the Screening Process of Fabry Disease: Analysis of Chronic Kidney Patients Not on Dialysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuri Battaglia ◽  
Fulvio Fiorini ◽  
Cristiano Azzini ◽  
Pasquale Esposito ◽  
Alessandro De vito ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Late Onset ◽  
Multiple Organ ◽  
Lysosomal Storage ◽  
Kidney Transplant Recipients ◽  
Screening Process ◽  
Efficient Treatment ◽  
Enzymatic Replacement Therapy ◽  
Gla Gene ◽  
Disease Analysis

Fabry Disease (FD), a rare and progressive, X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A (GLA) gene which leads to enzymatic deficiency of GLA. Misdiagnosed and undiagnosed FD cases are common for the variable FD phenotype, ranging from asymptomatic and/or impairment of single organs, which is typically seen in females and in patients with late-onset mutation, to multiple organ disease, which is frequently found in males with classic GLA mutation. Consequently, for an early diagnosis and an efficient treatment of FD, three different strategies of screening, new-born screening, high-risk screening and familiar screening, have been conducted. However, most of FD screening in the CKD population has been carried out in hemodialysis patients and kidney transplant recipients, for whom the renal damage is already irreversible, so the effectiveness of enzymatic replacement therapy is limited and delayed therapeutic intervention results in worse long-term outcomes. This review investigates the actual strategies of screening initiatives for the identification of FD, examining in detail those performed in CKD patients not on dialysis.

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