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Unexplained Fever In Hematologic Disorders Section 1. Benign Hematologic Disorders
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
Gaucher’s disease is a genetic disorder characterized by accumulation of glucocerebro-sides in the macrophages (Gaucher cells), due to the lack of glucosylceramidase activity. The infiltration of the spleen and the liver with these cells causes the enlargement of the organs. Fever may occur associated with bone pain and without evidence of infection.9 Pulmonary infiltrates may also be present. Splenomegaly may also be found in other storage diseases like Niemann-Pick disease, sea-blue histiocyte syndrome, etc.
Rare forms of interstitial lung disease
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
The most common lipid storage disorder is Gaucher disease, which is caused by a deficiency of a lysosomal enzyme glucocerebrosidase (also called glucosylceramidase) that leads to accumulation of glucocerebroside and other glycolipids within the lysosomes of macrophages and reticuloendothelial cells. The clinical manifestations of this disease result from accumulation of lipid-laden cells (i.e. Gaucher cells) in various organs, but the clinical severity of the disease varies widely. Most patients manifest hepatosplenomegaly, haematologic abnormalities and bone involvement.
An update on gene therapy for lysosomal storage disorders
Published in Expert Opinion on Biological Therapy, 2019
Murtaza S. Nagree, Simone Scalia, William M. McKillop, Jeffrey A. Medin
Outside of these two clinical trials, LV-based, HSC-directed, gene therapy is being investigated in animal models of other LSDs as well. While an early clinical attempt using γ-RV failed to generate long-term marking and engraftment of transduced CD34+ cells for the treatment of Gaucher disease [48], recent work using a recombinant LV as the delivery vehicle was successful in raising glucosylceramidase activity, clearing glucosylceramide buildup, and stopping the progression of Gaucher pathology in a mouse model of Type I Gaucher disease [49]. AVROBIO, Inc. has received a No Objection response from Health Canada to launch a phase I clinical trial based on this approach (AVRO-RD-02–201). This trial is expected to open in 2019.
The budget impact of enzyme replacement therapy in type 1 Gaucher disease in the United States
Published in Journal of Medical Economics, 2022
Sepehr Farahbakhshian, Timothy J. Inocencio, Gregory Poorman, Ekaterina Wright, Ravi Ramesh Pathak, Michael Bullano
Gaucher disease (GD) is a rare autosomal recessive condition resulting from mutations in the glucosylceramidase beta (GBA) gene encoding the glucosylceramidase enzyme1. The estimated prevalence of GD is 1 to 2 cases per 100,000 in the general population, with higher rates reported among people of Ashkenazi Jewish descent2. The estimated birth incidence of GD in the general population (including data from North America, Asia, Europe, Africa, and Australia) ranges from ∼0.39 to 5.80 cases per 100,000 births2.
Misconnecting the dots: altered mitochondrial protein-protein interactions and their role in neurodegenerative disorders
Published in Expert Review of Proteomics, 2020
Mara Zilocchi, Mohamed Taha Moutaoufik, Matthew Jessulat, Sadhna Phanse, Khaled A. Aly, Mohan Babu
Besides identifying the correct cellular model, integration of several omics approaches (genomic, transcriptomic, proteomic) will play a pivotal role in the investigation of the heterogeneous mechanisms in NDs, and in the discovery of a specific therapeutic treatment for each patient. For example, proteomic analysis on iPSC-derived neurons of Parkin-mutated patients revealed dysregulated mt proteins involved in oxidative stress defense, mt respiration, and mt morphology, cell cycle control and cell viability [141], providing insight into the effect of parkin dysfunction in PD-related pathways. Single-cell RNA-sequencing that has been utilized to decipher the heterogeneity in iPSC-derived dopaminergic neurons from PD patients carrying the glucosylceramidase beta risk variant (GBAN370S) identified downregulation of histone deacetylase 4 (HDAC4)-controlled genes, which was reversed by the treatment of HDAC4-modulating compounds that regulate mt dynamics, suggesting HDAC4 is a regulator of disease progression [136]. Despite single-cell gene expression changes generated to date for NDs [136,142,143], there is no clear understanding of how the dynamic reorganization and regional heterogeneity of the mt protein interactome, as well as the functional and pathologically affected brain regions, are connected to ND at the molecular level. Complete information regarding the organization of mtPPIs networks of the brain in ND patients is critical to: (1) comprehend the specialized biochemistry of different organelle compartments, cell types and regions that execute the distinctive capabilities of the brain tissue; (2) identify the mechanisms underlying ND pathogenesis; and (3) aid in the identification of new targets for therapeutic intervention. Most notably, the intra – and inter-individual variability of neurological diseases can be better elucidated by increasing the number of subjects investigated for a specific sporadic or familial ND, which will pave the way for the identification of biomarkers with high specificity for ND pathology [124].