• Acute kidney injury
• Cardiorenal syndrome
• Children
• Chronic kidney disease
• Systemic diseases

• Humans
• Cardio-Renal Syndrome/etiology
• Cardio-Renal Syndrome/therapy
• Cardio-Renal Syndrome/physiopathology
• Cardio-Renal Syndrome/diagnosis
• Cardio-Renal Syndrome/classification
• Child

• Anderson–Fabry disease
• arrhythmic risk stratification
• atrial fibrillation
• conduction system disorders
• sudden cardiac death
• tachyarrhythmias

• clinical trial results
• haematopoietic stem cells
• lysosomal storage disorders
• melphalan conditioning
• progenitor cells

• Humans
• Fabry Disease/therapy
• Fabry Disease/genetics
• Male
• Genetic Therapy/methods
• Lentivirus/genetics
• alpha-Galactosidase/genetics
• alpha-Galactosidase/therapeutic use
• Canada
• Adult
• Middle Aged
• Trihexosylceramides

• The Kidney Foundation of Canada
• MACC Fund
• AVROBIO, Inc
• 119187 CIHR
• Midwest Athletes Against Childhood Cancer
• Canadian Institutes of Health Research
• Midwest Athletes Against Childhood Cancer

• Fabry disease
• Risk factors
• Sudden cardiac death
• Ventricular fibrillation
• Ventricular tachycardia

• Humans
• Fabry Disease/complications
• Death, Sudden, Cardiac/prevention & control
• Death, Sudden, Cardiac/etiology
• Primary Prevention/methods
• Tachycardia, Ventricular/etiology
• Tachycardia, Ventricular/therapy
• Tachycardia, Ventricular/prevention & control
• Ventricular Fibrillation/prevention & control
• Ventricular Fibrillation/etiology
• Defibrillators, Implantable
• Risk Factors

• Humans
• Cardiomyopathy, Hypertrophic/therapy
• Cardiomyopathy, Hypertrophic/diagnosis

• Arrhythmia
• Atrial fibrillation
• Fabry
• Sudden cardiac death

• Fabry Disease/physiopathology
• Fabry Disease/complications
• Humans
• Arrhythmias, Cardiac/physiopathology
• Arrhythmias, Cardiac/etiology
• Death, Sudden, Cardiac/etiology
• Electrocardiography
• alpha-Galactosidase
• Risk Assessment

• MR/V009540/1 Medical Research Council

• Cardiomyopathies
• Clinical features
• Differences
• Management
• Outcomes
• Sex
• Women

• Humans
• Female
• Cardiomyopathies/therapy
• Cardiomyopathies/diagnosis
• Cardiomyopathies/physiopathology
• Cardiomyopathies/genetics
• Pregnancy
• Pregnancy Complications, Cardiovascular/therapy
• Pregnancy Complications, Cardiovascular/physiopathology
• Pregnancy Complications, Cardiovascular/diagnosis
• Pregnancy Complications, Cardiovascular/genetics
• Cardiomyopathy, Hypertrophic/therapy
• Cardiomyopathy, Hypertrophic/genetics
• Cardiomyopathy, Hypertrophic/diagnosis
• Cardiomyopathy, Hypertrophic/physiopathology
• Genetic Counseling/methods
• Disease Management

• Scuola Superiore Sant'Anna

• cardiovascular disorders of pregnancy
• genetic cardiomyopathy
• heart disease in women
• heart failure
• sex-related differences

• Male
• Humans
• Female
• United States
• Quality of Life
• Cardiomyopathies/diagnosis
• Cardiomyopathies/epidemiology
• Cardiomyopathies/genetics
• Heart Failure/diagnosis
• Heart Failure/epidemiology
• Heart Failure/therapy
• Sex Factors

• Anderson–Fabry disease
• cardiac involvement
• cardiomyopathy
• diagnostic red flags
• left ventricular dysfunction

• Fabry disease
• arrhythmia
• implantable loop recorder
• stroke
• sudden death

• CMR
• cardiovascular magnetic resonance
• echocardiography
• hypertrophy
• late gadolinium enhancement
• speckle tracking

• Fabry
• atrial fibrillation
• metabolic diseases
• pacemaker, artificial

• Adult
• Humans
• Bradycardia/diagnosis
• Bradycardia/epidemiology
• Bradycardia/etiology
• Atrial Fibrillation/diagnosis
• Atrial Fibrillation/epidemiology
• Atrial Fibrillation/therapy
• Fabry Disease/complications
• Fabry Disease/diagnosis
• Fabry Disease/epidemiology
• Incidence
• Pacemaker, Artificial/adverse effects

• Anderson-Fabry disease
• ECG pattern
• bundle branch block
• cardiac involvement
• electrocardiogram (ECG)
• left ventricular hyperertrophy
• repolarization abnormalities

• anderson-Fabry disease
• cardiac imaging
• enzyme replacement therapy
• heart failure
• management

• Bradycardia
• Fabry disease
• Permanent pacing
• Screening

• Arrhythmias
• Cardiovascular system
• Heart failure

• Cardiomyopathy, Hypertrophic/complications
• Cardiomyopathy, Hypertrophic/diagnosis
• Enzyme Replacement Therapy
• Fabry Disease/complications
• Fabry Disease/diagnosis
• Fabry Disease/genetics
• Humans
• Hypertrophy, Left Ventricular/diagnosis
• Hypertrophy, Left Ventricular/etiology
• Late Onset Disorders
• Male
• alpha-Galactosidase/genetics
• alpha-Galactosidase/therapeutic use

• Amyloidosis
• Fabry disease
• Hypertrophic cardiomyopathy
• Left ventricular hypertrophy
• Treatment of amyloidosis
• Treatment of left ventricular hypertrophy

Fabry disease (FD) is a rare, recessive X-linked, multisystemic lysosomal storage disorder (LSD) that results from a deficiency in the hydrolase alpha-galactosidase A (α-GalA) caused by a GLA gene variant. The progressive accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in organs such as skin, kidney, brain, joints, vascular walls and eyes are responsible for the wide spectrum of clinical manifestations, often unspecific. In result, clinically relevant and life-threatening complications, such as malignant ventricular arrhythmia, sudden cardiac death, end stage kidney failure and stroke may occur. In this review, we will describe the clinical features and the current perspectives in the multidisciplinary management Of FD patients.

• Conselho Nacional Pesquisa Desenvolvimento-Brasil

Fabry disease (FD) is an X-linked inherited disorder caused by mutations in the GLA gene encoding enzyme alpha-galactosidase A (α-Gal A). The purpose of this study was to produce a consensus statement to standardize the recommendations concerning kidney involvement in FD and provide advice on the diagnosis, screening, and treatment of adult and pediatric patients. This consensus document was organized from an initiative led by the Committee for Rare Diseases (Comdora) of the Brazilian Society of Nephrology (SBN). The review considered randomized clinical trials, real-world data studies, and the expertise of its authors. The purpose of this consensus statement is to help manage patient and physician expectations concerning the outcomes of treatment. Our recommendations must be interpreted within the context of available evidence. The decisions pertaining to each individual case must be made with the involvement of patients and their families and take into account not only the potential cost of treatment, but also concurrent conditions and personal preferences. The Comdora intends to update these recommendations regularly so as to reflect recent literature evidence, real-world data, and appreciate the professional experience of those involved. This consensus document establishes clear criteria for the diagnosis of FD and for when to start or stop specific therapies or adjuvant measures, to thus advise the medical community and standardize clinical practice.

• Anderson-Fabry disease
• Pacemaker
• bradyarrhythmias.

Fabry disease (FD) is an X‐linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi‐organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families.

Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G > A, c.811G > A, c.950T > C), 1 novel missense mutation (c.37G > C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre‐excitation occurred in 80% (4/5) of men and 16.7% (1/6) of women. Six patients (6/14, 42.9%) had chronic kidney disease with decreased renal function and all were male (6/7, 85.7%). Six patients presented with acroparesthesia, hypohidrosis, or both. Three female patients and two male patients experienced sudden death, and one male patient with the mutation (c.128G > A) died of progressive heart failure, between 41 and 66 years of age.

We reported five unrelated families of FD with different GLA mutations. Clinical manifestations were highly heterogeneous between male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long‐term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD.

• Fabry disease
• GLA gene
• Left ventricular hypertrophy
• Renal insufficiency

Fabry disease represents an X-linked inherited disorder resulting in the accumulation of globotriaosylceramide (Gb3). This review explains the clinical manifestations and the possible therapies for this condition. Fabry disease is considered the second most frequent lysosomal storage disease. More than 1000 mutations of the galactosidase alpha (GLA) gene associated with this disorder have been identified. Pain, either episodic crises or chronic pain, is one of the earliest symptoms in Fabry disease. Gastrointestinal, ocular, ear or skeletal manifestations may complete the clinical picture. Cardiac and renal involvements are the most severe complications leading to organ failure and death. The cerebrovascular lesions may result in severe symptoms including stroke at younger ages. The diagnosis of Fabry disease may be put by enzymatic assays of the α-galactosidase A (AGAL-A) activity in plasma or leukocytes but genetic analysis remains the “gold standard” in identifying the precise mutation and even guiding the treatment. Enzyme replacement therapy (ERT) was the first step in treating subjects with Fabry disease. It proved important decrease of the number of sever clinical events and reduction of symptoms. Chemical chaperone therapy has many advantages including oral administration and was already approved in Europe and US, but it is suitable only for subjects with amenable mutations. Gene therapies (either ex vivo or in vivo) promise to represent a new era for many disorders including Fabry disease, the preliminary data being encouraging. Although many steps were taken in understanding the pathogeny of Fabry disease, future research is needed especially in the field of therapeutic approaches.

• Fabry disease
• X chromosome inactivation
• carriers

• Fabry Disease/genetics
• Fabry Disease/pathology
• Female
• Heterozygote
• Humans
• Male
• Mutation
• Phenotype
• X Chromosome Inactivation
• alpha-Galactosidase/genetics

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder that results from a deficiency of α-galactosidase A enzyme activity in which glycosphingolipids gradually accumulate in multi-organ systems. Cardiac manifestations are the leading cause of mortality in patients with AFD. Among them, arrhythmias comprise a large portion of the heart disease cases in AFD, most of which are characterized by conduction disorders. However, atrial fibrillation as a presenting sign at the young age group diagnosed with AFD is uncommon.

We report a case of a 26-year-old man who was admitted with chest discomfort. Left ventricular hypertrophy was fulfilled in the criteria by the Sokolow-Lyon index and atrial fibrillation on the 12 Leads-electrocardiography (ECG) that was documented in the emergency room. After spontaneously restored to normal sinus rhythm, relationships between P and R waves, including a shorter PR interval on the ECG, were revealed. The echocardiographic findings showed thickened interventricular septal and left posterior ventricular walls. Based on the clues mentioned earlier, we realized the possibility of AFD. Additionally, we noticed the associated symptoms and signs, including bilateral mild hearing loss, neuropathic pain, anhidrosis, and angiokeratoma on the trunk and hands. He was finally diagnosed with classical AFD, which was confirmed by the gene mutation and abnormal enzyme activity of α-galactosidase A.

This case is a rare case of AFD as a presentation with atrial fibrillation at a young age. Confirming the relationship between P and Q waves on the ECG through sinus rhythm conversion may help in differential diagnosis of the cause of atrial fibrillation and hypertrophic myocardium.

• Fabry disease
• Atrial fibrillation
• Electrocardiography
• Cardioversion
• Glycosphingolipids
• Case report

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. Cardiac biomarkers, point-of-care dried blood spot testing, and advanced imaging modalities including echocardiography with strain imaging and magnetic resonance imaging (MRI) with T1 mapping now allow us to detect Fabry cardiomyopathy much more effectively than in the past. While enzyme replacement therapy (ERT) has been the mainstay of treatment, several promising therapies are now in development, making early diagnosis of FD even more crucial. Ongoing initiatives involving artificial intelligence (AI)-empowered interpretation of echocardiographic images, point-of-care dried blood spot testing in the echocardiography laboratory, and widespread dissemination of point-of-care ultrasound devices to community practices to promote screening may lead to more timely diagnosis of FD. Fabry disease should no longer be considered a rare, untreatable disease, but one that can be effectively identified and treated at an early stage before the development of irreversible end-organ damage.

• Fabry cardiomyopathy
• Fabry disease
• lysosomal storage disorder

• Fabry Disease/diagnosis
• Fabry Disease/therapy
• Humans

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.

• Fabry disease
• cardiomyopathy
• enzyme replacement therapy
• heart
• migalastat

• Cardiac innervation
• Cardiomyopathy
• Echo
• SPECT

• 3-Iodobenzylguanidine/pharmacokinetics
• Adult
• Fabry Disease/complications
• Fabry Disease/physiopathology
• Female
• Heart Ventricles/innervation
• Humans
• Male
• Middle Aged
• Radiopharmaceuticals/pharmacokinetics
• Sympathetic Nervous System/physiopathology
• Systole/physiology
• Tomography, Emission-Computed, Single-Photon
• Ventricular Dysfunction, Left/etiology
• Young Adult

Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD’s development and progression that could become useful targets for therapeutics. This review discusses FD’s cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage.

• cardiovascular disease
• fabry
• inflammation
• lysosomal disorder
• mitochondrial dysfunction

Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT).

Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined.

Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH.

Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.

• Fabry disease
• electrocardiogram (ECG)
• enzyme replacement therapy (ERT)
• gender difference
• left ventricular hypertrophy (LVH)

• Fabry disease
• biomarkers
• globotriaosylceramide (Gb3)
• podocyte injury
• urinary mulberry body

• COVID-19
• Fabry disease
• SARS-CoV-2
• chloroquine
• enzyme replacement therapy
• lysosome
• pathogenesis
• prevention

• FIS/FEDER
• KIDNEY ATTACK
• PERSTIGAN
• REDinREN
• Sociedad Española de Nefrología
• FRIAT
• Comunidad de Madrid en Biomedicina
• French ‘Plan National Maladies Rares’

• Cardiomyopathy
• Enzyme replacement therapy
• Fabry disease
• GLA gene

Fabry disease (FD) is one of the most common lysosomal storage disorders and is caused by an X-linked progressive inborn error of metabolism in the alpha-galactosidase A (α-Gal A) gene. This leads to intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), throughout the body. The impact of this accumulation is seen across multiple cell lines and therefore can cause multisystem organ dysfunction. The phenotype of FD results from variants on the GLA gene which codes for α-Gal A production, and variants on this gene have been shown to be strongly related to unexplained or idiopathic cardiovascular disorders. This report describes a 36-year-old Caucasian male found to have left ventricular hypertrophy (LVH) followed by genetic testing because of his family history of sudden cardiac death which revealed a variant of unknown significance for the GLA gene. Further measurement of α-Gal A leukocyte activity showed low levels, which was diagnostic for FD. The index patient had an unusual non-classic phenotype in that his sole presenting symptom was asymptomatic LVH, he presented early, and had low α-Gal A leukocyte activity. Early detection and prompt treatment with enzyme replacement therapy can improve outcomes and decrease mortality. In the absence of known risk factors, non-classical FD should be strongly considered in patients with unexplained LVH and a family history of sudden cardiac death at a young age.

• cardiac phenotype
• fabry disease
• left ventricular hypertrophy