• A family of mannosidases are also responsible for processing newly formed glycoproteins in the endoplasmic reticulum into mature glycoproteins containing highly heterogeneous complex-type glycans. (wikipedia.org)
  • More recently, the concept of lysosomal storage disease has been expanded to include deficiencies or defects in proteins necessary for the normal post-translational modification of lysosomal enzymes (which themselves are often glycoproteins), activator proteins, or proteins important for proper intracellular trafficking between the lysosome and other intracellular compartments. (medscape.com)
  • This enzyme catabolizes N-linked glycoproteins. (pictures-of-cats.org)
  • Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). (medlineplus.gov)
  • This enzyme is involved in the digestion of complex sugars derived from glycoproteins. (basepaws.com)
  • Lysosomal alpha-mannosidase is an exoglycosidase that cleaves alpha-linked mannose residues from the non-reducing end during the ordered degradation of N-linked glycoproteins. (jupiter.no)
  • The enzyme plays a role in the processing of newly formed N-glycans and in degradation of mature GLYCOPROTEINS. (harvard.edu)
  • EDEM3-CDG arises from an individual having mutations in both copies of their EDEM3 gene, which provides instructions for making an enzyme that helps ensure misfolded N-linked glycoproteins are broken down. (cdghub.com)
  • EDEM3 has mannosidase activity and can catalyze the removal of specific mannose sugars from the glycan chain of N-glycoproteins that are improperly folded. (cdghub.com)
  • EDEM3 is a part of a group of proteins (ER-1,2-alpha mannosidases or EDEMs) that possess mannosidase activity and can catalyze the removal of mannose sugar residues from the glycan chain of improperly folded N-glycoproteins. (cdghub.com)
  • There are two types: alpha-Mannosidase beta-Mannosidase A deficiency is associated with mannosidosis. (wikipedia.org)
  • Final Report Summary - ALPHA-MAN (Clinical development of Enzyme Replacement Therapy in alpha-Mannosidosis patients using recombinant human enzyme. (europa.eu)
  • The lysosomal storage disorder (LSD) alpha-Mannosidosis is a rare genetic disease and according to the EU regulations, designated as an "orphan" disease. (europa.eu)
  • Alpha-Mannosidosis is caused by an enzyme defect due to mutations in the gene for lysosomal alpha-Mannosidase (LAMAN) affecting the lysosomal and cellular glycoprotein catabolism with severe consequences for the organism. (europa.eu)
  • Today, the most promising therapy for lysosomal storage disorders including alpha-Mannosidosis is Enzyme Replacement Therapy (ERT) where the respective enzyme lacking in the patient is produced by recombinant approaches and then introduced into the blood stream, from where it is internalized by the cells and reaches the lysosomes replacing the missing endogenous enzyme. (europa.eu)
  • To date, no specific treatment for alpha-Mannosidosis is available. (europa.eu)
  • Since pharmaceutical interest in this disease is low, two EU-supported projects (EURAMAN and HUE-MAN) within the 5th and 6th framework program, respectively have worked towards developing the recombinant human enzyme (rhLAMAN) as a therapeutic agent for patients suffering from alpha-Mannosidosis. (europa.eu)
  • The final goal of ALPHA-MAN was to make a future treatment for ALL alpha-Mannosidosis patients available and thereby dramatically improving their life expectancy and quality of life. (europa.eu)
  • In line with our plans we have been able to demonstrate the safety and clinical efficacy of rhLAMAN as an effective therapeutic agent for treatment of the human disease alpha-Mannosidosis in clinical trial Phases 1 and 2. (europa.eu)
  • In non-clinical studies we also found the optimal rhLAMAN dose for a maximal correction of visceral and central nervous system pathology following injection in immune-tolerant alpha Mannosidosis mice. (europa.eu)
  • Putative receptors that are responsible for rhLAMAN uptake into the brain across the Blood Brain Barrier were investigated and we were able to study the outcome of long-term ERT on the neuropathology and associated behavioural deficits observed in immune-tolerant alpha-Mannosidosis mice. (europa.eu)
  • Alpha Mannosidosis is a rare inherited metabolic storage disease caused by a mutation in the gene for alpha-mannosidase, an enzyme that normally breaks down sugars (carbohydrates) in lysosomes. (ssa.gov)
  • Type III alpha mannosidosis is the most severe form, and signs and symptoms appear in infancy with rapid progression, severe neurological deterioration, and early death. (ssa.gov)
  • There is no cure or treatment to alter the progression of alpha-mannosidosis. (ssa.gov)
  • New and promising therapies for alpha mannosidosis include bone marrow transplantation, enzyme replacement, and gene therapy. (ssa.gov)
  • Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. (medlineplus.gov)
  • The signs and symptoms of alpha-mannosidosis can range from mild to severe. (medlineplus.gov)
  • Individuals with this early-onset form of alpha-mannosidosis often do not survive past childhood. (medlineplus.gov)
  • Other individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. (medlineplus.gov)
  • People with later-onset alpha-mannosidosis may survive into their fifties. (medlineplus.gov)
  • Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide. (medlineplus.gov)
  • Mutations in the MAN2B1 gene cause alpha-mannosidosis. (medlineplus.gov)
  • Tissues and organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell death, leading to the characteristic features of alpha-mannosidosis. (medlineplus.gov)
  • Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. (pediatricshealthcenter.com)
  • Alpha mannosidosis is a lysosomal storage disorder which results in the decreased efficiency of the production of an enzyme called alpha-D-mannosidase. (basepaws.com)
  • Mannosidosis is a group term for deficiencies in the enzyme mannosidase. (basepaws.com)
  • Depending on which of these enzymes is deficient, human mannosidosis is classified as α-mannosidosis or β-mannosidosis (U.S. National Library of Medicine, 2018). (basepaws.com)
  • Alpha mannosidosis is a lysosomal storage disorder which results in the deficiency of the production of the enzyme alpha-D-mannosidase. (basepaws.com)
  • Diagnosis of alpha-mannosidosis involves the detection of alpha-mannosidase enzyme activity in peripheral blood leukocytes, or white blood cells. (basepaws.com)
  • Long-term effective treatments for alpha-mannosidosis in cats have not been discovered yet. (basepaws.com)
  • Since long-term effective treatments for alpha-mannosidosis in cats have not been designed yet, it is not recommended to breed from mutation carriers in order to prevent the succession of the genetic anomaly to kittens. (basepaws.com)
  • A webinar series dedicated to spotting the early signs of alpha-mannosidosis (AM), an ultra-rare genetic disorder caused by a deficiency of the lysosomal enzyme alpha-mannosidase. (ineip.org)
  • The symptoms, severity, and progression of alpha-mannosidosis vary widely between individuals, making diagnosis challenging and often delayed. (ineip.org)
  • Minimising the time to diagnosis is important in ensuring that individuals with alpha-mannosidosis and their families receive timely access to support and specialist MDT care. (ineip.org)
  • Join our experts as they explore the diverse symptoms of alpha-mannosidosis, challenges and solutions for timely diagnosis, and best practices for long-term management and multidisciplinary care. (ineip.org)
  • The FDA has started a priority review of Chiesi 's velmanase alfa, an enzyme replacement therapy for lysosomal storage disease (LSD) alpha-mannosidosis, with a decision expected in the first half of 2023. (nxtpsychedelics.com)
  • Patients with alpha-mannosidosis are typically diagnosed in childhood and experience a wide range of symptoms, including infections, hearing loss and poor eyesight, muscle weakness, skeletal and joint problems, and cognitive abnormalities. (nxtpsychedelics.com)
  • Mark Stark, treasurer at the International Society for Mannosidosis & Related Disorders (ISMRD) and father of a son living with alpha-mannosidosis, said the prospect of a first treatment for the disease "is bringing patients, parents, families and caregivers hope for a better future. (nxtpsychedelics.com)
  • He added: "As someone who knows personally how devastating alpha-mannosidosis can be, this is an important milestone toward a potential first treatment option that addresses the root cause of the disease. (nxtpsychedelics.com)
  • Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. (beds.ac.uk)
  • Alpha-mannosidosis is an autosomal recessive lysosomal storage disease characterized by mental retardation, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency. (beds.ac.uk)
  • Classification Systems Two classification systems have been used to describe the clinical presentation of alpha-mannosidosis. (beds.ac.uk)
  • Performing regular review of the literature on alpha-Mannosidosis mutations and their functional impact. (jupiter.no)
  • Performing research on the spectrum of alpha-Mannosidosis mutations, as well as on the impact of mutations on enzyme activity, structure, processing, localization and clinical features. (jupiter.no)
  • Alpha-mannosidosis is lysosomal storage disorder caused by deficiency of lysosomal alpha mannosidase ( MAN2B1 ). (jupiter.no)
  • Alpha-mannosidosis is inherited in an autosomal recessive manner . (jupiter.no)
  • Defects in the lysosomal form of the enzyme results in a buildup of mannoside intermediate metabolites and the disease ALPHA-MANNOSIDOSIS. (harvard.edu)
  • Alpha -mannosidosis is a lysosomal storage disease. (medicinelearners.com)
  • Alpha-mannosidosis is an extremely rare disease. (medicinelearners.com)
  • The cause of α-mannosidosis lies in the inability of the enzyme α-mannosidase to function. (medicinelearners.com)
  • α-Mannosidosis can be diagnosed by determining the enzyme activity of α-mannosidase. (medicinelearners.com)
  • If the activity of this enzyme in the leukocytes is very low, it is an α-mannosidosis. (medicinelearners.com)
  • This gene provides instructions for making the enzyme alpha-mannosidase. (medlineplus.gov)
  • Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down mannose-containing oligosaccharides. (medlineplus.gov)
  • Deficiency of alpha-mannosidase in cats is associated with an autosomal recessive mutation in the lysosomal alpha-mannosidase gene ( LAMAN ), although there are confirmations that different mutations may occur in certain cases (Berg et al, 1997). (basepaws.com)
  • tested the efficacy of cisterna magna infusion of adeno-associated virus type 1 (AVV1) expressing a healthy feline alpha-mannosidase gene in the affected cat. (basepaws.com)
  • The EDEM3 gene encodes the enzyme ER degradation enhancing alpha-mannosidase like protein 3 (EDEM3). (cdghub.com)
  • The gene encoding this enzyme is known as the MAN2B1 gene and is located on chromosome 19. (medicinelearners.com)
  • The gene defect, which leads to the failure of α-mannosidase, is inherited in an autosomal recessive manner. (medicinelearners.com)
  • Fabry disease is caused by a mutation of the alpha-galactosidase A gene ( GLA ) mapped to the long arm of the X chromosome [5]. (dermnetnz.org)
  • Overall, this study reveals the impact of cln5 -deficiency on gene expression in D. discoideum , provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease. (frontiersin.org)
  • In E. coli , Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ. (wikidoc.org)
  • This enzyme has a molecular mass of 73.6 kDa, and is coded for by the gene glgX. (wikidoc.org)
  • Classically, lysosomal storage diseases encompassed only enzyme deficiencies of the lysosomal hydrolases. (medscape.com)
  • Therefore, the enzyme activity of multiple lysosomal hydrolases is increased in plasma and other body fluids. (ggc.org)
  • Glycoside hydrolases that catalyze the hydrolysis of alpha or beta linked MANNOSE . (lookformedical.com)
  • In general, exposure to BL delayed tomato seed germination in a fluency rate-dependent way due to negative impacts on the activities of endosperm-degrading hydrolases, such as endo-ß-mannanase, ß-mannosidase, and α-galactosidase. (bvsalud.org)
  • This enzyme is involved in the hydrolysis of the sugar mannose and can be found in two forms: α (alpha) and β (beta). (basepaws.com)
  • An enzyme that catalyzes the HYDROLYSIS of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. (harvard.edu)
  • An enzyme that catalyzes the hydrolysis of an alpha L-fucoside to yield an alcohol and L-fucose. (jefferson.edu)
  • Diseases caused by the loss of one or more enzymes involved in the hydrolysis of mannoside linkages (MANNOSIDASES). (ouhsc.edu)
  • A group of enzymes that catalyze the hydrolysis of alpha- or beta-xylosidic linkages. (nih.gov)
  • Other xylosidases have been identified that catalyze the hydrolysis of alpha-xylosidic bonds. (nih.gov)
  • In humans, LAMAN deficiency results in progressive mental retardation, skeletal changes, hearing loss and recurrent infections and many patients die during early childhood. (europa.eu)
  • Deficiency in EDEM3 results in decreased removal of mannose residues and accumulation of misfolded proteins. (cdghub.com)
  • Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates , however they are not considered lectins . (lookformedical.com)
  • RNA enzymes may observe from also translocated proteins, they may phosphorylate suggested in proteins with delayed strategies, or they may outline known in membranes of factor factors. (evakoch.com)
  • Proteins that catalyze both functions are referred to as glycogen debranching enzymes (GDEs). (wikidoc.org)
  • The following information is freely available as a service to the scientific community: Published data on disease causing mutations and benign polymorphisms and their effect on enzyme activity, protein conformation, processing and localization. (jupiter.no)
  • [1] When glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as Glycogen storage disease type III can result. (wikidoc.org)
  • Defining a new immune deficiency syndrome: MAN2B2-CDG. (harvard.edu)
  • Due to the immune deficiency, numerous poorly healing infections can occur in the first years of life, which in turn have a formative effect on the general course of the disease. (medicinelearners.com)
  • Enzyme replacement therapy (ERT) appears safe and effective for peripheral manifestations in patients with Gaucher disease types I and III, Fabry disease, mucopolysaccharidosis I (Hurler, Hurler-Scheie, and Scheie syndromes), mucopolysaccharidosis II (Hunter syndrome), mucopolysaccharidosis VI (Maroteaux-Lamy syndrome), Pompe disease, and recently Batten disease (neuronal ceroid lipofuscinoses, CLN2). (medscape.com)
  • Enzyme replacement therapy (ERT) appears safe and effective for peripheral manifestations in patients with Gaucher disease types I and III, Fabry disease, mucopolysaccharidosis I (Hurler, Hurler-Scheie, and Scheie syndromes), mucopolysaccharidosis II (Hunter syndrome), mucopolysaccharidosis VI (Maroteaux-Lamy syndrome), and Pompe disease. (medscape.com)
  • Results from diagnostic enzyme assays in peripheral blood cells, or in cultured fibroblast cells, should be included. (jupiter.no)
  • When genetic variants relevant to a patient are then detected via CentoMetabolic MOx, we automatically complement the analysis with biomarkers and/or enzyme testing if applicable, and include the results in the medical report. (centogene.com)
  • The defects in enzyme activity are primarily associated with genetic mutation of the genes that codes for a particular mannosidase isoenzyme. (ouhsc.edu)
  • In this study, we used comparative transcriptomics to identify differentially expressed genes underlying cln5 -deficiency phenotypes during growth and the early stages of multicellular development. (frontiersin.org)
  • Previous work in mammalian models reported altered lysosomal enzyme activity due to mutation or loss of CLN5 . (frontiersin.org)
  • The vanishingly rare, progressive and debilitating disease is caused by a deficiency in the enzyme alpha-mannosidase, leading to a build-up of complex sugars that damage the central nervous system and organs of the body. (nxtpsychedelics.com)
  • However, if the protein is not folded correctly, the enzyme UDP-glucose: glycoprotein glucosyltransferase (UGGT) will re-add a glucose molecule to the glycan chain 6 . (cdghub.com)
  • [9] A second protein, referred to as debranching enzyme, performs α-1,6-glucose cleavage. (wikidoc.org)
  • A confirmed diagnosis is documented by abnormally low or absent levels of alpha-D-mannosidase enzymatic activity in white blood cells. (ssa.gov)
  • Enzyme activity can be measured in dried blood spots. (ggc.org)
  • Origin of a-mannosidase activity in CSF. (harvard.edu)
  • Enzyme activity is profoundly decreased in all tissues tested. (beds.ac.uk)
  • Enzyme activity is deficient in red blood cells (RBC) and circulating white blood cells, but normal or near normal in all other tissues. (beds.ac.uk)
  • Enzyme activity is deficient in red blood cells and circulating white blood cells and less than 50% of normal levels in other cells tested. (beds.ac.uk)
  • A debranching enzyme is a molecule that helps facilitate the breakdown of glycogen , which serves as a store of glucose in the body, through glucosyltransferase and glucosidase activity. (wikidoc.org)
  • [10] Activity of the two enzymes is not always necessarily coupled. (wikidoc.org)
  • The enzyme alpha-galactosidase A catalyses the cleavage (separation) of the terminal galactose from Gb3. (dermnetnz.org)
  • Any member of the class of enzymes that catalyze the cleavage of the glycosidic linkage of glycosides and the addition of water to the resulting molecules. (bvsalud.org)
  • Thus the debranching enzymes, transferase and α-1,6- glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase. (wikidoc.org)
  • In complexes, the other enzymes affect cleaved CBF1( or RBPJkappa), while in channels they are required Lag-1, immediately that the m ' CSL ' demonstrates separated been to this produced feature experience breast. (evakoch.com)
  • Glucosyltransferase and glucosidase are performed by a single enzyme in mammals, yeast, and some bacteria, but by two distinct enzymes in E. coli and other bacteria, complicating nomenclature. (wikidoc.org)
  • In E. coli and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct enzymes. (wikidoc.org)
  • Amylo-α-1,6-glucosidase ( EC 3.2.1.33 ), or glucosidase , cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen. (wikidoc.org)
  • When glucosyltransferase and glucosidase are catalyzed by distinct enzymes, "glycogen debranching enzyme" usually refers to the glucosidase enzyme . (wikidoc.org)
  • Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood. (lookformedical.com)
  • Epimerase deficiency galactosemia (GALE deficiency galactosemia) is generally considered a continuum comprising several forms: Generalized. (beds.ac.uk)
  • Lack of the alpha-galactosidase A enzyme leads to accumulation of Gb3 in various tissues, leading to cell death. (dermnetnz.org)
  • Here, we detected altered intracellular activities of various carbohydrate enzymes and cathepsins during cln5 - growth and starvation. (frontiersin.org)
  • Intracellular lectins and glycan-modifying enzymes mediate autophagy and control host immunity and inflammation. (nature.com)
  • Over time, that effort crystallised around rare diseases, and in 2018 the company added pegunigalsidase alfa, an investigational enzyme replacement therapy for Fabry disease developed by Israel's Protalix BioTherapeutics that is due to be filed for approval before the end of this year. (nxtpsychedelics.com)
  • Prenatal diagnosis and carrier testing via enzyme analysis are not available. (ggc.org)
  • Efforts are underway to develop enzyme replacement options for several other disorders. (medscape.com)
  • Mucolipidosis II (ML II), also known as I-Cell disease, and Mucolipidosis IIIA (ML IIIA), also known as Pseudo-Hurler Polydystrophy, are lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-1-phosphotransferase (NAPT). (ggc.org)
  • In ML II and ML IIIA, lysosomal hydrolase enzymes are not properly targeted to the lysosome. (ggc.org)
  • This has led to active clinical trials evaluating the safety and efficacy of intrathecal enzyme delivery in several lysosomal storage diseases (see www.ClinicalTrials.gov ). (medscape.com)
  • TWIK was canonical thrombus tempered K+ mannosidases occur characterised by investigation in the Respiratory formation. (familie-vos.de)
  • The assay uses 4-methylumbelliferyl substrates to measure the activities of acid sphingomyelinase, alpha-iduronidase, beta-glucosidase, and alpha-mannosidase. (ggc.org)
  • These acids and bases are amino acid side chains in the active site of the enzyme. (wikidoc.org)
  • alpha-Mannosidase" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • Mannosidase Deficiency Diseases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ouhsc.edu)
  • Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. (lookformedical.com)
  • In Persian kittens, this deficiency has been associated with stillbirths and neonatal death (Cummings et al, 1988). (basepaws.com)
  • Human brain ABCA1 deficiency boosts BBB dysfunction after heart stroke To check whether human brain ABCA1 insufficiency regulates BBB leakage after heart stroke, albumin and AQP4 appearance in the ischemic human brain were assessed. (bioinf.org)