Histiocytosis and Lipid Storage Diseases
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
e. Nervous System. Gaucher cells are present in perivascular Virchow-Robin spaces in the brain parenchyma. There is widespread neuronal loss; dentate nucleus of cerebellum is almost always involved. Multiple myeloma, chronic lymphocytic leukemia, and amyloidosis are associated with Gaucher’s disease more commonly than in the normal population. Pregnancy is not contraindicated, but is considered to be high risk because of thrombocytopenia, and coagulation defects that might lead to bleeding. Pseudo-Gaucher cells are morphologically similar to Gaucher cells, but do not contain tubular structures characteristic of the Gaucher cells. These can be seen in various conditions, e.g., acute lymphoblastic leukemia, multiple myeloma, chronic granulocytic leukemia, plasmacytoid lymphoma, Hodgkin’s lymphoma, and AIDS with Mycobacterium avium infection. Patients with Gaucher’s disease receiving alglucerase treatment show a false-positive pregnancy test, as alglucerase is a placenta-derived drug and contains human chorionic gonadotrophin.
Gaucher disease
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Gaucher disease was the first lysosomal storage disease for which this approach became available. The major breakthrough in permitting successful therapy was the recognition that lipid-laden macrophages have a mannose receptor [87]; modifying the glycoprotein glucocerebrosidase to expose a terminal mannose permits the enzyme to attach to and be incorporated into the macrophage [48]. A modified form of the enzyme purified from human placenta was approved for treatment in 1991 under the name Ceredase (algucerase), and then in 1994, a form of human glucocerebrosidase produced in cultured Chinese hamster ovary cells was approved under the name Cerezyme (imiglucerase). This has largely replaced alglucerase. Another form, produced in human fibroblasts, was approved in 2010 under the name VPRIV (velaglucerase).
Pulmonary hypertension induced by drugs and toxins
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Gaucher’s disease is an autosomal-recessive disorder that is caused by a deficiency of the enzyme glucocerebrosidase. PAH has been detected in patients with type 1 Gaucher’s disease. This may be due at least in part to perivascular infiltration by Gaucher’s cells with vascular obliteration and plugging of the capillaries with Gaucher’s cells. However, three cases of PAH have been reported to be associated with the use of alglucerase after eliminating the possible involvement of Gaucher’s cells.61,62
Pharmacological treatment of pediatric Gaucher disease
Published in Expert Review of Clinical Pharmacology, 2018
Punita Gupta, Gregory Pastores
Alglucerase was subsequently replaced by human recombinant imiglucerase (CerezymeTM, Sanofi/Genzyme), generated using Chinese hamster ovary (CHO) cells, in the mid-1990s; this preparation continues to be the most widely used ERT in clinics across the world. In 2009, a vesivirus 2117 infection of the bioreactors in which imiglucerase was manufactured led to a global shortage of imiglucerase and expedited the approval of two ‘new’ enzymes: gene-activated human recombinant velaglucerase alfa (VPRIVTM, Shire) derived from a human fibrosarcoma cell line and plant-cell-derived human recombinant taliglucerase alfa (ElelysoTM Protalix/Pfizer). All three recombinant enzyme formulations have exposed mannosyl-residues, although the process involved in achieving this is unique for each product. These three ERTs are not biosimilar products, and there appears to be no major difference in their safety profile [45–48].
Related Knowledge Centers
- Biopharmaceutical
- Gaucher'S Disease
- Glucocerebrosidase
- Enzyme
- Oligosaccharide
- Mannose
- Residue
- Citric Acid
- Buffer Solution
- Tissue