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Erlenmeyer Flask Deformity
Published in Michael E. Mulligan, Classic Radiologic Signs, 2020
Philippe Gaucher1 described the condition that now bears his name in 1882. This cerebroside disorder leads to packing of the bone marrow with lipid-laden reticuloendothelial cells and causes modeling abnormalities that are especially well demonstrated in the metaphyses of the long bones. The earliest detailed descriptions of the clinical, radiologic and pathologic findings were presented in two separate articles2,3, from the same case material, in 1926. The radiologist involved, Sven Junghagen (Rontgeninstitut Lund), described the abnormal contour of the ends of the long bones in a 3-year-old girl who had clinical and radiographic follow up over a 2-year period. However, it was A.W. Fisher (University of Frankfurt) who seems to have first used the term flask-shaped (flaschenformige) in an article 2 years later4 (Figure 1). He discussed the long bone changes, especially those in the distal femur, in 16 cases. Nine of the patients had a diagnosis of Gaucher’s disease. The others had diagnoses that included: Picks disease, chronic osteomyelitis, arthritis deformans and pernicious anemia. Fisher emphasized that the differences and similarities between cases, that may occur in the shape of the distal femur, are dependent upon the specific disease process involved. Thus, this Erlenmeyer flask-shaped deformity is not specific for Gaucher’s disease. It can be seen with many other disorders especially marrow-packing disorders. The long bone radiographic changes in what is now known as Niemann-Pick’s disease are indistinguishable from those due to Gaucher’s disease.
Gaucher disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Gaucher disease is inherited in an autosomal recessive fashion. Most patients are of type 1, and this is most common in Ashkenazi Jews, in whom the incidence has been estimated at between one in 640 [24] and one in 855 [74]. This is the most prevalent genetic disorder in that population.
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.
Dual enzyme therapy improves adherence to chemotherapy in a patient with gaucher disease and Ewing sarcoma
Published in Pediatric Hematology and Oncology, 2023
Brandon Lucari, Eran Tallis, Vernon Reid Sutton, Timothy Porea
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme acid beta-glucocerebrosidase (GBA). Deficient hydrolase activity results in the accumulation of glucosylceramide in phagocytes.1 Three variants of GD are reported, with type 1 being the most prevalent with an occurrence of 1:40,000 in the general population.2 Key clinical manifestations of type 1 GD are visceromegaly, hematologic abnormalities, and bone crisis secondary to an inflammatory response of lipid laden macrophage deposition into tissue sites.1 Less common phenotypes types 2 and 3 are defined by the presence of neurologic involvement.3 Diagnosis is confirmed by analysis of glucocerebrosidase activity in peripheral leukocytes and sequencing of the GBA gene.4
N-Methyl-D-Aspartate (NMDA) receptor modulators: a patent review (2015-present)
Published in Expert Opinion on Therapeutic Patents, 2020
Hazem Ahmed, Ahmed Haider, Simon M. Ametamey
Gaucher’s disease (GD) is a genetic disorder caused by a mutation in the GBA1 gene and is the most common out of the 50 lysosomal storage diseases. A patent filed by Yeda Research and Development Company in 2015 claimed the use of established NMDA receptor antagonists in treating the neuropathic forms of GD, i.e., type 2 and 3 [237]. Using 15 different mouse strains, the inventors discovered that GRIN2B polymorphisms are associated with the life expectancy of GD mice, and that administering an NMDA receptor antagonist surprisingly increased their life span [238]. They unraveled a single nucleotide variation (SNP ID rs29869040) in the non-coding area of the GRIN2B that correlated with GD prognosis. In addition, they showed that NMDA receptor agonists such as D-cycloserine reduced survival rate contrary to NMDA receptor antagonists (dizocilpine, memantine, and ifenprodil) which increased the GD mice life span. NMDA receptor antagonists claimed were not necessarily selective toward NMDA receptors, for example concurrently targeting sigma-1 receptors, neither only toward a specific subunit. The claim list included memantine, nitromemantine, neramexane, ketamine, amantadine, dextromethorphan, traxoprodil, ifenprodil, and Ro 25–6981 amongst others, whether alone or as a combination therapy.
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.