scholarly journals Biomarkers in Anderson–Fabry Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8080
Author(s):  
Irene Simonetta ◽  
Antonino Tuttolomondo ◽  
Mario Daidone ◽  
Antonio Pinto
Keyword(s):  
Fabry Disease ◽  
Lysosomal Storage Disorder ◽  
Screening Tool ◽  
Clinical Course ◽  
Response To Treatment ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Plasma Proteome ◽  
Lysosomal Storage ◽  
Clinical Progression

Fabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This review aims to summarise the current evidence and knowledge about general and specific markers that are actually measured in subjects with confirmed or suspected Fabry disease; moreover, we report potential novel markers such as microRNAs. Recent proteomic or metabolomic studies are in progress bringing out plasma proteome profiles in Fabry patients: this assessment may be useful to characterize molecular pathology of the disease, to improve diagnostic process, and to monitor response to treatment. The management of Fabry disease may be improved by the identification of biomarkers that reflect clinical course, severity, and the progression of the disease.

scholarly journals Sweat Gland Biopsy: A Possible Early Diagnostic Tool in the Anderson-Fabry Disease

2016 ◽  
Author(s):  
Giuseppe Pistone ◽  
Valentina Caputo ◽  
Davide Fattore ◽  
Giovanna Tilotta ◽  
Maria Rita Bongiorno
Keyword(s):  
Fabry Disease ◽  
Vascular Endothelium ◽  
Lysosomal Storage Disorder ◽  
Systemic Disease ◽  
Gastrointestinal Symptoms ◽  
Sweat Glands ◽  
Lysosomal Storage ◽  
Morphological Diagnosis ◽  
Cornea Verticillata ◽  
Early Diagnostic

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

scholarly journals Gene therapy in Anderson- Fabry disease. State of the art and future perspectives

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giorgio Spiniello ◽  
Federica Verrillo ◽  
Riccardo Ricciolino ◽  
Dario Prozzo ◽  
Andrea Tuccillo ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Fabry Disease ◽  
Lysosomal Storage Disorder ◽  
State Of The Art ◽  
Single Gene ◽  
Lysosomal Storage ◽  
Future Perspectives ◽  
Enzyme Replacement ◽  
Potential Benefits ◽  
Number Of Cells

Anderson Fabry disease (AFD) is an Xlinked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, agalactosidase A. The inadequate enzymatic activity leads to systemic storage of glycosphingolipids, mostly globotriaosylceramide, in the lysosomes. As of now, enzyme replacement therapy is the only approved treatment for AFD. However, it does not induce a complete and lasting response in several clinical contexts. Genemediated enzyme replacement is an emerging approach that could overcome these limits. The single gene nature of AFD enhances the possibility to transfect and modify a small number of cells, making them capable to affect the correction of a larger number of cells. This review summarizes the history and the state of the art of gene therapy in AFD, showing potential benefits and limits.

COVID-19 in children: Pathogenesis and current status

2020 ◽  
Author(s):  
Lawrence Frenkel ◽  
Fernando Gomez ◽  
Joseph A Bellanti
Keyword(s):  
Respiratory Disease ◽  
Respiratory Symptoms ◽  
Distress Syndrome ◽  
Clinical Course ◽  
Current Status ◽  
Current Evidence ◽  
Initial Description ◽  
Relationship Of ◽  
Inflammatory Syndrome ◽  
The Relationship

Background: Since its initial description in December 2019 in Wuhan, China, coronavirus disease 2019 (COVID-19) has rapidly progressed into a worldwide pandemic, which has affected millions of lives. Unlike the disease in adults, the vast majority of children with COVID-19 have mild symptoms and are largely spared from severe respiratory disease. However, thereare children who have significant respiratory disease, and some may develop a hyperinflammatory response similar to thatseen in adults with COVID-19 and in children with Kawasaki disease (KD), which has been termed multisystem inflammatory syndrome in children (MIS-C).Objective: The purpose of this report was to examine the current evidence that supports the etiopathogenesis of COVID-19 in children and the relationship of COVID-19 with KD and MIS-C as a basis for a better understanding of the clinical course, diagnosis, and management of these clinically perplexing conditions.Results: The pathogenesis of COVID-19 is carried out in two distinct but overlapping phases of COVID-19: the first triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and the second by the host immune response. Children with KD have fewer of the previously described COVID-19–associated KD features with less prominent acute respiratory distress syndrome and shock than children with MIS-C.Conclusion: COVID-19 in adults usually includes severe respiratory symptoms and pathology, with a high mortality. Ithas become apparent that children are infected as easily as adults but are more often asymptomatic and have milder diseasebecause of their immature immune systems. Although children are largely spared from severe respiratory disease, they canpresent with a SARS-CoV-2–associated MIS-C similar to KD.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

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