scholarly journals Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases

2019 ◽  
Vol 20 (2) ◽  
pp. 327 ◽  
Author(s):  
Paola Faverio ◽  
Anna Stainer ◽  
Federica De Giacomi ◽  
Serena Gasperini ◽  
Serena Motta ◽  
...  
Keyword(s):  
Sleep Apnea Syndrome ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Airway Disease ◽  
Pulmonary Involvement ◽  
Molecular Pathways ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Obstructive Sleep ◽  
Wide Range

Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Pulmonary involvement includes interstitial lung disease in Gaucher’s disease and Niemann-Pick disease, obstructive airway disease in Fabry disease and ventilatory disorders with chronic respiratory failure in Pompe disease due to diaphragmatic and abdominal wall muscle weakness. In mucopolysaccharidosis and mucolipidoses, respiratory symptoms usually manifest early in life and are secondary to anatomical malformations, particularly of the trachea and chest wall, and to accumulation of glycosaminoglycans in the upper and lower airways, causing, for example, obstructive sleep apnea syndrome. Although the molecular pathways involved vary, ranging from lipid to glycogen and glycosaminoglycans accumulation, some clinical manifestations and therapeutic approaches are common among diseases, suggesting that lysosomal storage and subsequent cellular toxicity are the common endpoints.

scholarly journals Lysosomal Leukodystrophies Lysosomal Storage Diseases Associated With White Matter Abnormalities

2019 ◽  
Vol 34 (6) ◽  
pp. 339-358 ◽  
Author(s):  
Gustavo H.B. Maegawa
Keyword(s):  
White Matter ◽  
Metabolic Diseases ◽  
Age Groups ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Abnormal Development ◽  
Neurologic Manifestations ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Extrapyramidal Signs

The leukodystrophies are a group of genetic metabolic diseases characterized by an abnormal development or progressive degeneration of the myelin sheath. The myelin is a complex sheath composed of several macromolecules covering axons as an insulator. Each of the leukodystrophies is caused by mutations in genes encoding enzymes that are involved in myelin production and maintenance. The lysosomal storage diseases are inborn disorders of compartmentalized cellular organelles with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes and related organelles. The more than 60 different lysosomal storage diseases are rare diseases; however, collectively, the incidence of lysosomal storage diseases ranges just over 1 in 2500 live births. The majority of lysosomal storage diseases are associated with neurologic manifestations including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. These inborn organelle disorders show wide clinical variability affecting individuals from all age groups. In addition, several of neurologic, also known as neuronopathic, lysosomal storage diseases are associated with some level of white matter disease, which often triggers the diagnostic investigation. Most lysosomal storage diseases are autosomal recessively inherited and few are X-linked, with females being at risk of presenting with mild, but clinically relevant neurologic manifestations. Biochemical assays are the basis of the diagnosis and are usually confirmed by molecular genetic testing. Novel therapies have emerged. However, most affected patients with lysosomal storage diseases have only supportive management to rely on. A better understanding of the mechanisms resulting in the leukodystrophy will certainly result in innovative and efficacious disease-modifying therapies.

scholarly journals Macroglossia, Motor Neuron Pathology, and Airway Malacia Contribute to Respiratory Insufficiency in Pompe Disease: A Commentary on Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases

2019 ◽  
Vol 20 (3) ◽  
pp. 751 ◽  
Author(s):  
Angela McCall ◽  
Mai ElMallah
Keyword(s):  
Motor Neuron ◽  
Respiratory Insufficiency ◽  
Pompe Disease ◽  
Lysosomal Storage Diseases ◽  
Molecular Pathways ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Respiratory Involvement

The authors of the recently published, “Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases”, provide an important review of the various mechanisms of lysosomal storage diseases (LSD) and how they culminate in similar clinical pathologies [...]

scholarly journals System for computer diagnosis of hereditary diseases

2020 ◽  
pp. 9-11
Author(s):  
Б.А. Кобринский ◽  
Н.А. Благосклонов ◽  
Н.С. Демикова
Keyword(s):  
Differential Diagnosis ◽  
Decision Support ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Hereditary Diseases ◽  
Lysosomal Storage ◽  
Computer Diagnosis ◽  
Storage Diseases ◽  
Intellectual System ◽  
Expert Assessments

В работе описаны принципы создания компьютерной консультативной системы поддержки принятия решений при диагностике наследственных заболеваний на долабораторном этапе. Прототип реализуется на примере клинических проявлений лизосомных болезней накопления. В основу системы положены литературные данные, которые сопровождаются оценками экспертов. Разрабатываемая интеллектуальная система формирует ограниченный дифференциально-диагностический ряд гипотез. Это обеспечивает помощь врачу-генетику в дифференциальной диагностике как при наличии у него предварительного диагноза, так и при отсутствии у него предположений о нозологии заболевания. The paper describes the principles of creating a computer consultative decision support system for the diagnosis of hereditary diseases at the pre-laboratory stage. The prototype is implemented on the example of the clinical manifestations of lysosomal storage diseases. The system is based on literary data, which are accompanied by expert assessments. The developed intellectual system forms a limited differential diagnostic row of hypotheses. It provides assistance to the geneticist in differential diagnosis both in the presence of a preliminary diagnosis and in the absence of assumptions about the nosology of the disease.

Visual representation of knowledge about the clinical signs of lysosomal storage diseases

2020 ◽  
pp. 65-69
Author(s):  
E. V. Titova ◽  
Keyword(s):  
Knowledge Engineering ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Negative Effect ◽  
Engineering Information ◽  
Appropriate Therapy ◽  
Representation Of Knowledge

The article discusses the representation of information on lysosomal storage diseases to support the process of diagnostic decisions in childhood. This hereditary pathology refers to rare (orphan) diseases that are difficult to recognize and without timely appropriate therapy has a negative effect on the quality and expectancy of life. The article analyzes information sources for 16 nosological units from this group. Using the methods of knowledge engineering, information about the identified clinical manifestations is represented in the form of visual portraits (mind map) for diagnostics diseases and improvement qualification of pediatricians.

scholarly journals Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Silvia Parolo ◽  
Danilo Tomasoni ◽  
Pranami Bora ◽  
Alan Ramponi ◽  
Chanchala Kaddi ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Acid Sphingomyelinase ◽  
Cytokine Signaling ◽  
Literature Mining ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Inflammatory Signals

Lysosomal storage diseases (LSDs) are characterized by the abnormal accumulation of substrates in tissues due to the deficiency of lysosomal proteins. Among the numerous clinical manifestations, chronic inflammation has been consistently reported for several LSDs. However, the molecular mechanisms involved in the inflammatory response are still not completely understood. In this study, we performed text-mining and systems biology analyses to investigate the inflammatory signals in three LSDs characterized by sphingolipid accumulation: Gaucher disease, Acid Sphingomyelinase Deficiency (ASMD), and Fabry Disease. We first identified the cytokines linked to the LSDs, and then built on the extracted knowledge to investigate the inflammatory signals. We found numerous transcription factors that are putative regulators of cytokine expression in a cell-specific context, such as the signaling axes controlled by STAT2, JUN, and NR4A2 as candidate regulators of the monocyte Gaucher disease cytokine network. Overall, our results suggest the presence of a complex inflammatory signaling in LSDs involving many cellular and molecular players that could be further investigated as putative targets of anti-inflammatory therapies.

scholarly journals Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications

2021 ◽  
Vol 22 (18) ◽  
pp. 10064
Author(s):  
Valentina La Cognata ◽  
Maria Guarnaccia ◽  
Giovanna Morello ◽  
Martino Ruggieri ◽  
Agata Polizzi ◽  
...  
Keyword(s):  
Ad Hoc ◽  
Diagnostic Delay ◽  
Clinical Manifestations ◽  
Cost Effective ◽  
Lysosomal Storage Diseases ◽  
Turnaround Time ◽  
Diagnostic Methods ◽  
Standard Group ◽  
Lysosomal Storage ◽  
Storage Diseases

Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the approval of disease-specific therapies and the rapid emergence of novel rapid diagnostic methods has opened, for a set of selected LSDs, the possibility for inclusion in extensive national newborn screening (NBS) programs. Herein, we evaluated the clinical utility and diagnostic validity of a targeted next-generation sequencing (tNGS) panel (called NBS_LSDs), designed ad hoc to scan the coding regions of six genes (GBA, GAA, SMPD1, IDUA1, GLA, GALC) relevant for a group of LSDs candidate for inclusion in national NBS programs (MPSI, Pompe, Fabry, Krabbe, Niemann Pick A-B and Gaucher diseases). A standard group of 15 samples with previously known genetic mutations was used to test and validate the entire flowchart. Analytical accuracy, sensitivity, and specificity, as well as turnaround time and costs, were assessed. Results showed that the Ion AmpliSeq and Ion Chef System-based high-throughput NBS_LSDs tNGS panel is a fast, accurate, and cost-effective process. The introduction of this technology into routine NBS procedures as a second-tier test along with primary biochemical assays will allow facilitating the identification and management of selected LSDs and reducing diagnostic delay.

Electron Microscopy in the diagnosis of lysosomal storage diseases

1989 ◽  
Vol 47 ◽  
pp. 866-867
Author(s):  
Carole Vogler ◽  
Harvey S. Rosenberg
Keyword(s):  
Electron Microscopy ◽  
Lysosomal Enzyme ◽  
Rectal Mucosa ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Storage Material ◽  
Ultrastructural Examination ◽  
Blood Leukocytes ◽  
Storage Diseases

Diagnostic procedures for evaluation of patients with lysosomal storage diseases (LSD) seek to identify a deficiency of a responsible lysosomal enzyme or accumulation of a substance that requires the missing enzyme for degradation. Most patients with LSD have progressive neurological degeneration and may have a variety of musculoskeletal and visceral abnormalities. In the LSD, the abnormally diminished lysosomal enzyme results in accumulation of unmetabolized catabolites in distended lysosomes. Because of the subcellular morphology and size of lysosomes, electron microscopy is an ideal tool to study tissue from patients with suspected LSD. In patients with LSD all cells lack the specific lysosomal enzyme but the distribution of storage material is dependent on the extent of catabolism of the substrate in each cell type under normal circumstances. Lysosmal storages diseases affect many cell types and tissues. Storage material though does not accumulate in all tissues and cell types and may be different biochemically and morphologically in different tissues.Conjunctiva, skin, rectal mucosa and peripheral blood leukocytes may show ultrastructural evidence of lysosomal storage even in the absence of clinical findings and thus any of these tissues can be used for ultrastructural examination in the diagnostic evaluation of patients with suspected LSD. Biopsy of skin and conjunctiva are easily obtained and provide multiple cell types including endothelium, epithelium, fibroblasts and nerves for ultrastructural study. Fibroblasts from skin and conjunctiva can also be utilized for the initiation of tissue cultures for chemical assays. Brain biopsy has been largely replaced by biopsy of more readily obtained tissue and by biochemical assays. Such assays though may give equivical or nondiagnostic results and in some lysosomal storage diseases an enzyme defect has not yet been identified and diagnoses can be made only by ultrastructural examination.

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