Agalsidase alfa long-term effect on left ventricular hypertrophy in Fabry disease.

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left ventricular hypertrophy (LVH), leading to early death due to complications (arrhythmias, valvular disease, vascular involvement). Early initiation of enzyme replacement therapy (ERT) before fibrosis development has been associated with better cardiac outcomes in terms of left ventricular mass index (LVMI) and functional parameters.

The role of tubular cells in the pathogenesis of Fabry nephropathy.

The pathophysiology of Fabry nephropathy (FN) is induced by galactosidase A deficiency with a chronic exposure of glycolipids to every lineage of renal cells. Tissue damage is attributed to the activation of molecular pathways, resulting in tissue fibrosis and chronic kidney disease. Podocytes have been the primary focus in clinical pathophysiological research because of the striking accumulation of large glycolipid deposits observable in histology.

Pathogenic pathways of renal damage in Fabry nephropathy: interplay between immune cell infiltration, apoptosis and fibrosis.

Background: Fabry nephropathy is a consequence of the deposition of globotriaosylceramide, caused by deficient GLA enzyme activity in all types of kidney cells. These deposits are perceived as damage signals leading to activation of inflammation resulting in renal fibrosis. There are few studies related to immunophenotype characterization of the renal infiltrate in kidneys in patients with Fabry disease and its relationship to mechanisms of fibrosis.

Exploring the Pathophysiologic Cascade Leading to Osteoclastogenic Activation in Gaucher Disease Monocytes Generated via CRISPR/Cas9 Technology.

Gaucher disease (GD) is caused by biallelic pathogenic variants in the acid β-glucosidase gene (), leading to a deficiency in the β-glucocerebrosidase (GCase) enzyme activity resulting in the intracellular accumulation of sphingolipids. Skeletal alterations are one of the most disabling features in GD patients. Although both defective bone formation and increased bone resorption due to osteoblast and osteoclast dysfunction contribute to GD bone pathology, the molecular bases are not fully understood, and bone disease is not completely resolved with currently available specific therapies.

Opportunities and challenges for newborn screening and early diagnosis of rare diseases in Latin America.

Rare diseases (RDs) cause considerable death and disability in Latin America. Still, there is no consensus on their definition across the region. Patients with RDs face a diagnostic odyssey to find a correct diagnosis, which may last many years and creates a burden for caregivers, healthcare systems, and society.

Screening for Fabry disease in Argentina in male patients with chronic kidney disease at all stages.

We report three patients diagnosed with Fabry disease through a screening study which included individuals suffering from chronic kidney disease (CKD) at any stage. The study recruited 1740 male patients, and three Fabry patients were diagnosed, resulting in a frequency of 0.17%.

Major cardiovascular adverse events in Fabry disease patients receiving agalsidase alfa.

Cardiovascular mortality (CVM) has become the major contributor to overall Fabry disease (FD) mortality in the enzyme replacement therapy (ERT) era. Our objectives were to describe causes and potential predictors of mortality in FD adult patients in Argentina, and to assess risk of major adverse cardiovascular events (MACE) in the ERT era. We retrospectively studied 93 consecutive patients treated with alphagalactosidase A (median follow up: 9.

Pathology and pathogenic pathways in fabry nephropathy.

Background: The pathophysiology of renal damage in Fabry nephropathy involves a complex biological mechanism. The intracellular deposition globotriaosylceramide (Gb3) is just the first step of the mechanism. The glycolipid deposition occurs in all renal cells (endothelial, epithelial and mesangial cells).

[Early diagnosis of Gaucher disease based on bone symptoms].

Gaucher disease (GD) is caused by a genetic deficiency of the lysosomal enzyme glucocerebrosidase (GCase) leading to the accumulation of glucocerebroside in the liver, spleen, and bone marrow. The early diagnosis allows a prompt enzyme replacement therapy reversing cytopenias and visceromegaly and preventing irreversible bone lesions. Current diagnostic algorithms are based on well-recognized hematological manifestations.

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

Objectives: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation.

Design And Setting: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs.

Upregulation of ASIC1a channels in an in vitro model of Fabry disease.

Neuropathic pain is one of the key features of the classical phenotype of Fabry disease (FD). Acid sensing ion channels (ASICs) are H-gated cation channels, which belong to the epithelial sodium channel/DeGenerin superfamily, sensitive to the diuretic drug Amiloride. Molecular cloning has identified several distinct ASIC subunits.

CRISPR/Cas9 Editing for Gaucher Disease Modelling.

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the acid β-glucosidase gene (). Besides causing GD, mutations constitute the main genetic risk factor for developing Parkinson's disease. The molecular basis of neurological manifestations in GD remain elusive.

Pathogenesis of Fabry nephropathy: The pathways leading to fibrosis.

Background: Kidney is one of the main target organs in Fabry disease, a lysosomal X-linked genetic disorder. Renal involvement is characterized by proteinuria and progressive chronic kidney disease leading to end-stage renal disease. Pathogenic mechanisms in the progression of renal damage in Fabry disease are not thoroughly known yet.

Fabry pedigree analysis: A successful program for targeted genetic approach.

Background: Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). FD is still an underdiagnosed disorder worldwide. Moreover, there is delay between symptom onset and Fabry diagnosis of at least 10 years.

Efficacy of pentosan polysulfate in in vitro models of lysosomal storage disorders: Fabry and Gaucher Disease.

Gaucher and Fabry diseases are the most prevalent sphingolipidoses. Chronic inflammation is activated in those disorders, which could play a role in pathogenesis. Significant degrees of amelioration occur in patients upon introduction of specific therapies; however, restoration to complete health status is not always achieved.

A Comprehensive Study of Bone Manifestations in Adult Gaucher Disease Type 1 Patients in Argentina.

Gaucher disease (GD) is the most prevalent lysosomal storage disease, and bone involvement is the most disabling condition. The aim of the present study was to evaluate bone involvement in adult patients with GD, using an observational cross-sectional study. Patients were evaluated using X-rays, bone densitometry (BMD), trabecular bone score (TBS), magnetic resonance imaging (MRI), and biochemical bone markers.

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina.

Methods: This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015.

Contribution of inflammatory pathways to Fabry disease pathogenesis.

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated.

Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update.

Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic disease with significant morbidity and mortality in children and adults. This document provides guidance on when to suspect LAL-D and how to diagnose it. It is recommended to add lysosomal acid lipase deficiency to the List of differential diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea, chronic malnutrition, and hemophagocytic lymphohistiocytosis.

Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease.

Gaucher disease (GD) is caused by mutations in the glucosylceramidase β () gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement.

Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System.

Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal.

Apical left ventricular hypertrophy and mid-ventricular obstruction in fabry disease.

We report the case of a rare cardiac presentation of Fabry disease. Although concentric left ventricular hypertrophy is a major cardiac finding in Fabry disease, there is no case report of dynamic obstruction at mid-left ventricular level. We describe a 59-year-old-woman suffering from a severe form of Fabry disease, mimicking an apical hypertrophic cardiomyopathy with mid-ventricular obstruction.

[Guidelines for diagnosis, monitoring and treatment of Fabry disease].

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease.

Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of Gaucher disease.

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Type I GD is the mildest form and is characterized by the absence of neuronopathic affection.