Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease.

Introduction: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood.

Diagnosis of Fabry Disease Using Alpha-Galactosidase A Activity or LysoGb3 in Blood Fails to Identify Up to Two Thirds of Female Patients.

Anderson-Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase A. The GLA gene is located on the X-chromosome, causing an X-linked pathology: due to lyonization, female patients usually manifest a variable symptomatology, ranging from asymptomatic to severe phenotypes. The confirmation of the clinical diagnosis of Fabry disease, achieved by measuring α-galactosidase A activity, which is usually the first test used, shows differences between male and female patients.

Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis.

Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis.

Corrigendum: Case report: mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson-Fabry disease.

[This corrects the article DOI: 10.3389/fgene.2023.

Case report: mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson-Fabry disease.

Anderson-Fabry disease (AFD) is an X-linked disease that results from reduced activity of the enzyme galactosidase alpha (GLA). When the GLA gene sequence is altered by mutations that alter the normal DNA sequence, variants of the alpha-galactosidase A enzyme are produced, which may or may not function. These mutations are responsible for Fabry disease, and to date, over 800 different mutations of the gene have been described in patients with Anderson-Fabry disease.

Sex Differences in Anderson-Fabry Cardiomyopathy: Clinical, Genetic, and Imaging Analysis in Women.

Anderson-Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease's X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS).

Gaucher disease prevalence in 600 patients affected by monoclonal gammopathy of undetermined significance.

Background: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists.

Patients And Methods: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022.

GM Allotypes and COVID-19. A Pilot Study Performed on Sicilian Patients.

Several studies suggest that genetic variants that influence the onset, maintenance and resolution of the immune response might be fundamental in predicting the evolution of COVID-19. In the present paper, we analysed the distribution of GM allotypes (the genetic markers of immunoglobulin γ chains) in symptomatic and asymptomatic COVID-19 patients and in healthy controls, all born and residing in Sicily. Indeed, the role played by GM allotypes in immune responses and infection control is well known.

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population.

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands.

Hemochromatosis Mimicked Gaucher Disease: Role of Hyperferritinemia in Evaluation of a Clinical Case.

Gaucher disease is a disorder of lysosomes caused by a functional defect of the glucocerebrosidase enzyme. The disease is mainly due to mutations in the GBA1 gene, which determines the gradual storage of glucosylceramide substrate in the patient's macrophages. In this paper, we describe the case of a 38-year-old man who clinically presented with hyperferritinemia, thrombocytopenia, leukopenia, anemia and mild splenomegaly; a diagnosis of hemochromatosis was made 10 years earlier.

How Important Are Genes to Achieve Longevity?

Several studies on the genetics of longevity have been reviewed in this paper. The results show that, despite efforts and new technologies, only two genes, APOE and FOXO3A, involved in the protection of cardiovascular diseases, have been shown to be associated with longevity in nearly all studies. This happens because the genetic determinants of longevity are dynamic and depend on the environmental history of a given population.

miR-126-3p and miR-21-5p as Hallmarks of Bio-Positive Ageing; Correlation Analysis and Machine Learning Prediction in Young to Ultra-Centenarian Sicilian Population.

Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which are potentially predictors of biological age. They can be used as a biomarker of risk for age-related inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and ECs senescence that seem to be characteristic of the healthy ageing phenotype.

A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19.

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant.

Healthy ageing and Mediterranean diet: A focus on hormetic phytochemicals.

Mediterranean diet (MedDiet) is rich in fruits and vegetables associated with longevity and a reduced risk of several age-related diseases. It is demonstrated that phytochemicals in these plant products enhance the positive effects of MedDiet by acting on the inflammatory state and reducing oxidative stress. Evidence support that these natural compounds act as hormetins, triggering one or more adaptive stress-response pathways at low doses.

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this "cytokine storm" and why the male older population is more severely affected, are currently unanswered questions.

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience.

Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease.

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker.

DNA methylation impact on Fabry disease.

Background: Fabry disease (FD) is a rare X-linked disease caused by mutations in GLA gene with consequent lysosomal accumulation of globotriaosylceramide (Gb3). Women with FD often show highly heterogeneous symptoms that can manifest from mild to severe phenotype.

Main Body: The phenotypic variability of the clinical manifestations in heterozygous women with FD mainly depends on the degree and direction of inactivation of the X chromosome.

Pompe disease: pathogenesis, molecular genetics and diagnosis.

Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized on chromosome 17 and encoding for acid alpha-1,4-glucosidase (GAA). Currently, more than 560 mutations spread throughout gene have been reported. GAA catalyzes the hydrolysis of α-1,4 and α-1,6-glucosidic bonds of glycogen and its deficiency leads to lysosomal storage of glycogen in several tissues, particularly in muscle.

Prevalence of GLA gene mutations and polymorphisms in patients with multiple sclerosis: A cross-sectional study.

Purpose: Fabry Disease (FD) has been frequently proposed as possible underestimated differential diagnosis of Multiple Sclerosis (MS), but no study has been performed to test prevalence of GLA gene mutations in a population fulfilling diagnostic criteria of MS. Aim of this study is to determine the prevalence of GLA gene mutations in a large and representative population diagnosed with MS, simultaneously providing a critical revision of current literature reports of coexistence or misdiagnosis between these two conditions.

Methods: In this mono-centric cross-sectional study, 927 patients fulfilling McDonald diagnostic criteria and encompassing all MS phenotypes were enrolled.

Circulating miRNAs in Successful and Unsuccessful Aging. A Mini-review.

Aging is a multifactorial process that affects the organisms at genetic, molecular and cellular levels. This process modifies several tissues with a negative impact on cells physiology, tissues and organs functionality, altering their regeneration capacity. The chronic low-grade inflammation typical of aging, defined as inflammaging, is a common biological factor responsible for the decline and beginning of the disease in age.

The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans.

Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture.

Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis.

Background: Tissue evaluation for RAS (KRAS or NRAS) gene status in metastatic colorectal cancer (mCRC) patients represent the standard of care to establish the optimal therapeutic strategy. Unfortunately, tissue biopsy is hampered by several critical limitations due to its invasiveness, difficulty to access to disease site, patient's compliance and, more recently, neoplastic tissue spatial and temporal heterogeneity.

Methods: The authors performed a systematic literature review to identify available trials with paired matched tissue and ctDNA RAS gene status evaluation.