Carbohydrate Metabolism, Inborn Errorsalpha-Mannosidosis: An inborn error of metabolism marked by a defect in the lysosomal isoform of ALPHA-MANNOSIDASE activity that results in lysosomal accumulation of mannose-rich intermediate metabolites. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder.Mannosidases: Glycoside hydrolases that catalyze the hydrolysis of alpha or beta linked MANNOSE.DisaccharidasesMannose: A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed)alpha-Mannosidase: An enzyme that catalyzes the HYDROLYSIS of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. The enzyme plays a role in the processing of newly formed N-glycans and in degradation of mature GLYCOPROTEINS. There are multiple isoforms of alpha-mannosidase, each having its own specific cellular location and pH optimum. Defects in the lysosomal form of the enzyme results in a buildup of mannoside intermediate metabolites and the disease ALPHA-MANNOSIDOSIS.Swainsonine: An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.Cat Diseases: Diseases of the domestic cat (Felis catus or F. domesticus). This term does not include diseases of the so-called big cats such as CHEETAHS; LIONS; tigers, cougars, panthers, leopards, and other Felidae for which the heading CARNIVORA is used.Cattle Diseases: Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.Oligosaccharides: Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Integrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Integrin alpha6beta4: This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.Integrin alpha Chains: The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Integrin alpha1: An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.Alpha Rhythm: Brain waves characterized by a relatively high voltage or amplitude and a frequency of 8-13 Hz. They constitute the majority of waves recorded by EEG registering the activity of the parietal and occipital lobes when the individual is awake, but relaxed with the eyes closed.Integrin alpha3: An integrin alpha subunit that occurs as alternatively spliced isoforms. The isoforms are differentially expressed in specific cell types and at specific developmental stages. Integrin alpha3 combines with INTEGRIN BETA1 to form INTEGRIN ALPHA3BETA1 which is a heterodimer found primarily in epithelial cells.alpha 1-Antitrypsin Deficiency: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.PPAR alpha: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Hepatocyte Nuclear Factor 1-alpha: Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Kinetics: The rate dynamics in chemical or physical systems.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.alpha Karyopherins: Nucleocytoplasmic transport molecules that bind to the NUCLEAR LOCALIZATION SIGNALS of cytoplasmic molecules destined to be imported into the CELL NUCLEUS. Once attached to their cargo they bind to BETA KARYOPHERINS and are transported through the NUCLEAR PORE COMPLEX. Inside the CELL NUCLEUS alpha karyopherins dissociate from beta karypherins and their cargo. They then form a complex with CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN and RAN GTP-BINDING PROTEIN which is exported to the CYTOPLASM.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.
Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis. (1/56)
Alpha-mannosidosis is a lysosomal storage disease with autosomal recessive inheritance caused by a deficiency of the lysosomal alpha-mannosidase, which is involved in the degradation of asparagine-linked carbohydrate cores of glycoproteins. An alpha-mannosidosis mouse model was generated by targeted disruption of the gene for lysosomal alpha-mannosidase. Homozygous mutant animals exhibit alpha-mannosidase enzyme deficiency and elevated urinary secretion of mannose-containing oligosaccharides. Thin-layer chromatography revealed an accumulation of oligosaccharides in liver, kidney, spleen, testis and brain. The cellular alterations were characterized by multiple membrane-limited cytoplasmic vacuoles as seen for instance in liver, exocrine pancreas, kidney, thyroid gland, smooth muscle cells, osteocytes and in various neurons of the central and peripheral nervous systems. The morphological lesions and their topographical distribution, as well as the biochemical alterations, closely resemble those reported for human alpha-mannosidosis. This mouse model will be a valuable tool for studying the pathogenesis of inherited alpha-mannosidosis and may help to evaluate therapeutic approaches for lysosomal storage diseases. (+info)Glycoprotein lysosomal storage disorders: alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency. (2/56)
Glycoproteinoses belong to the lysosomal storage disorders group. The common feature of these diseases is the deficiency of a lysosomal protein that is part of glycan catabolism. Most of the lysosomal enzymes involved in the hydrolysis of glycoprotein carbohydrate chains are exo-glycosidases, which stepwise remove terminal monosaccharides. Thus, the deficiency of a single enzyme causes the blockage of the entire pathway and induces a storage of incompletely degraded substances inside the lysosome. Different mutations may be observed in a single disease and in all cases account for the nonexpression of lysosomal glycosidase activity. Different clinical phenotypes generally characterize a specific disorder, which rather must be described as a continuum in severity, suggesting that other biochemical or environmental factors influence the course of the disease. This review provides details on clinical features, genotype-phenotype correlations, enzymology and biochemical storage of four human glycoprotein lysosomal storage disorders, respectively alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency. Moreover, several animal disorders of glycoprotein metabolism have been found and constitute valuable models for the understanding of their human counterparts. (+info)Lysosomal storage disease caused by Sida carpinifolia poisoning in goats. (3/56)
A neurologic disease characterized by ataxia, hypermetria, hyperesthesia, and muscle tremors of the head and neck was observed for 2 years in a flock of 28 Anglo-Nubian and Saanen goats on a farm with 5 ha of pasture. Six newborns died during the first week of life, and five abortions were recorded. The predominant plant in the pasture was Sida carpinifolia. The disease was reproduced experimentally in two goats by administration of this plant. Three goats with spontaneous disease and the two experimental animals were euthanatized and necropsied. No significant gross lesions were observed. Fragments of several organs, including the central nervous system, were processed for histopathology. Small fragments of the cerebellar cortex, liver, and pancreas of two spontaneously poisoned goats and two experimentally poisoned goats were processed for electron microscopy. Multiple cytoplasm vacuoles in hepatocytes, acinar pancreatic cells, and neurons, especially Purkinje cells, were the most striking microscopic lesions in the five animals. Ultrastructural changes included membrane-bound vacuoles in hepatocytes, Kupffer cells, acinar pancreatic cells, Purkinje cells, and the small neurons of the granular cell layer of the cerebellum. Paraffin-embedded sections of the cerebellum and pancreas were submitted for lectin histochemical analysis. The vacuoles in different cerebellar and acinar pancreatic cells reacted strongly to the following lectins: Concanavalia ensiformis, Triticum vulgaris, and succinylated Triticum vulgaris. The pattern of staining, analyzed in Purkinje cells and acinar pancreatic cells coincides with results reported for both swainsonine toxicosis and inherited mannosidosis. (+info)Recent progress in lysosomal alpha-mannosidase and its deficiency. (4/56)
Lysosomal alpha-mannosidase (EC 3.2.1.24) is a major exoglycosidase in the glycoprotein degradation pathway. A deficiency of this enzyme causes the lysosomal storage disease, alpha-mannosidosis, which has been described in humans, cattle, domestic cats and guinea pigs. Recently, great progress has been made in studying the enzyme and its deficiency. This includes cloning of the gene encoding the enzyme, characterization of mutations related to the disease, establishment of valuable animal models, and encouraging results from bone marrow transplantation experiments. (+info)alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis. (5/56)
alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal alpha-mannosidase. We report here the sequencing and expression of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant alpha-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human alpha-mannosidosis. (+info)Alpha-mannosidosis and mutational analysis in a Turkish patient. (6/56)
We present a case of alpha-mannosidosis with its mutational analysis. She was referred to our hospital with the provisional diagnosis of mucolipidosis. She was the first child of second-degree relative parents. She had a coarse face with flat and wide nasal bridge, hepatosplenomegaly, umbilical hernia, lumbar gibbus, motor and mental retardation and deafness. On peripheral blood smear, lymphocytes revealed vacuoles and neutrophils contained some granules resembling Reilly bodies seen in mucopolysaccharidosis (MPS). Based on these findings, the diagnosis of alpha-mannosidosis was suspected. Her urine oligosaccharide chromatography showed an abnormal pattern with a heavy trisaccharide band. Enzyme studies on white cells confirmed a deficiency of alpha-mannosidase activity, which was 2.6 micromol/g/hr. Her DNA analysis showed a S453Y mutation. (+info)Bovine plasma beta-mannosidase activity and its potential use for beta-mannosidosis carrier detection. (7/56)
Plasma beta-mannosidase activities were determined for Salers cattle from 8 herds as an evaluation of this method for detection of beta-mannosidosis heterozygotes. Several biological factors, such as age, gender, herd, and risk of being a beta-mannosidosis carrier, were considered in this study. The mean enzyme activity for obligate heterozygotes (n = 8) was 55 U/ml (range = 43-65 U/ml), which was 59% of the mean enzyme activity for cattle that were low risk for being a carrier. These data indicate that bovine beta-mannosidosis is characterized by a gene dosage effect. The analytical and biological variation of plasma beta-mannosidase activity that was observed necessitates limiting the test to adult fullblood/purebred Salers cattle within a herd. Plasma beta-mannosidase analysis provides important information for intraherd selection of Salers cattle that are heterozygous for beta-mannosidosis. (+info)Intracellular transport of human lysosomal alpha-mannosidase and alpha-mannosidosis-related mutants. (8/56)
Human LAMAN (lysosomal a-mannosidase) was synthesized as a 120 kDa precursor in transfected COS cells [African-green-monkey kidney cells], which was partly secreted as a single-chain form and partly sorted to the lysosomes being subsequently cleaved into three peptides of 70, 40 and 15 kDa respectively. Both the secreted and the lysosomal forms contained endo H (endoglucosidase H)-resistant glycans, suggesting a common pathway through the trans-Golgi network. A fraction of LAMAN was retained intracellularly as a single-chain endo H-sensitive form, probably in the ER (endoplasmic reticulum). The inherited lack of LAMAN causes the autosomal recessive storage disease a-mannosidosis. To understand the biochemical consequences of the disease-causing mutations, 11 missense mutations and two in-frame deletions were introduced into human LAMAN cDNA by in vitro mutagenesis and the resulting proteins were expressed in COS cells. Some selected mutants were also expressed in Chinese-hamster ovary cells. T355P (Thr355Pro), P356R, W714R, R750W and L809P LAMANs as well as both deletion mutants were misfolded and arrested in the ER as inactive single-chain forms. Six of the mutants were transported to the lysosomes, either with less than 5% of normal specific activity (H72L, D196E/N and R220H LAMANs) or with more than 30% of normal specific activity (E402K LAMAN). F320L LAMAN resulted in much lower activity in Chinese-hamster ovary cells when compared with COS cells. Modelling into the three-dimensional structure revealed that the mutants with highly reduced specific activities contained substitutions of amino acids involved in the catalysis, either co-ordinating Zn2+ (His72 and Asp196), stabilizing the active-site nucleophile (Arg220) or positioning the active-site residue Asp319 (Phe320). (+info)LMNA Mannosidosis, alpha-, types I and II; 248500; MAN2B1 Mannosidosis, beta; 248510; MANBA Maple syrup urine disease, type Ia ... RAG1 Alpha-2-plasmin inhibitor deficiency; 262850; PLI Alpha-ketoglutarate dehydrogenase deficiency; 203740; OGDH Alpha- ... NLRP3 Mucolipidosis II alpha/beta; 252500; GNPTAB Mucolipidosis III alpha/beta; 252600; GNPTAB Mucolipidosis III gamma; 252605 ... methylacetoacetic aciduria; 203750; ACAT1 Alpha-thalassemia myelodysplasia syndrome, somatic; 300448; ATRX Alpha-thalassemia ...
... and skeletal abnormalities in children with alpha-mannosidosis. After beginning to provide clinical services for children with ... "Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients". Bone Marrow Transplant. 47 (3): 352-9. doi: ...
The plant contains the alkaloid swainsonine causing alpha-mannosidosis, a risk to grazing livestock. In 2014, thousands of ...
There are two types: alpha-Mannosidase beta-Mannosidase A deficiency is associated with mannosidosis. A family of mannosidases ...
"Alpha-mannosidosis.". Orphanet J Rare Dis 3: 21. PMC 2515294. PMID 18651971. doi:10.1186/1750-1172-3-21. ... alpha-Mannosidase na US National Library of Medicine Medical Subject Headings (MeSH) ... GeneReviews/NCBI/NIH/UW entry on Alpha-Mannosidosis. *OMIM entries on Alpha-Mannosidosis ...
GeneReviews/NCBI/NIH/UW entry on Alpha-Mannosidosis OMIM entries on Alpha-Mannosidosis alpha-Mannosidase at the US National ... alpha-Mannosidase (EC 3.2.1.24, alpha-D-mannosidase, p-nitrophenyl-alpha-mannosidase, alpha-D-mannopyranosidase, 1,2-alpha- ... exo-alpha-mannosidase) is an enzyme involved in the cleavage of the alpha form of mannose. Its systematic name is alpha-D- ... Malm D, Nilssen Ø (2008). "Alpha-mannosidosis". Orphanet J Rare Dis. 3: 21. doi:10.1186/1750-1172-3-21. PMC 2515294 . PMID ...
... alpha-mannosidosis, Klippel-Trenaunay-Weber syndrome, cardiofaciocutaneous syndrome, Ras pathway disorders, transient neonatal ...
Wolman disease Oligosaccharide Alpha-mannosidosis Beta-mannosidosis Aspartylglucosaminuria Fucosidosis Lysosomal transport ... gangliosidoses Alpha-galactosidase Fabry disease (alpha-galactosidase A) Schindler disease (alpha-galactosidase B) Beta- ... Locoweed Mannosidosis Molecular chaperone therapy Winchester B, Vellodi A, Young E (2000). "The molecular basis of lysosomal ...
... alpha-mannosidosis MeSH C18.452.648.202.607.750 --- beta-mannosidosis MeSH C18.452.648.202.670 --- mucolipidoses MeSH C18.452. ... alpha-mannosidosis MeSH C18.452.648.595.577.750 --- beta-mannosidosis MeSH C18.452.648.595.600 --- mucopolysaccharidoses MeSH ...
... alpha-mannosidosis MeSH C16.320.565.202.607.750 --- beta-mannosidosis MeSH C16.320.565.202.670 --- mucolipidoses MeSH C16.320. ... alpha-mannosidosis MeSH C16.320.565.580.577.750 --- beta-mannosidosis MeSH C16.320.565.580.600 --- mucopolysaccharidoses MeSH ... alpha-thalassemia MeSH C16.320.070.875.150 --- beta-thalassemia MeSH C16.320.077.090 --- anemia, diamond-blackfan MeSH C16.320. ... alpha-thalassemia MeSH C16.320.365.826.100.350 --- hydrops fetalis MeSH C16.320.365.826.150 --- beta-thalassemia MeSH C16.320. ...
Fucosidosis Aspartylglucosaminuria Alpha-mannosidosis Other Wolman disease (acid lipase deficiency) Immunodeficiencies T-cell ...
Acromegaly Alpha-mannosidosis type II Aspartylglycosaminuria Battaglia Neri syndrome Borjeson Syndrome Chromosome 6q deletion ... alpha B lysosomal) McCune-Albright Syndrome Mental retardation (X-linked - epilepsy - progressive joint contractures - typical ... Immunodeficiency due to defect in MAPBP-interacting protein Infantile sialic acid storage disorder Job syndrome Mannosidosis ( ...
... and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a ... The enzyme catalyzes the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, ... A domain, which is found in the central region adopts a structure consisting of three alpha helices, in an immunoglobulin/ ... The domain is predominantly found in the enzyme alpha-mannosidase. Henrissat B, Callebaut I, Mornon JP, Fabrega S, Lehn P, ...
... is a deficiency in mannosidase, an enzyme. There are two types: Alpha-mannosidosis Beta-mannosidosis Swainsonine ... Mannosidosis at the US National Library of Medicine Medical Subject Headings (MeSH). ...
Beta-mannosidase Alpha-mannosidosis "Mannosidosis, beta A, lysosomal , Genetic and Rare Diseases Information Center (GARD) - an ... via lectin histochemistry to distinguish between α-mannosidosis and beta-mannosidosis. In terms of beta-mannosidosis treatment ... Beta-mannosidosis is inherited in an autosomal recessive manner. Affected individuals appear normal at birth, and can have a ... "beta-mannosidosis". Genetics Home Reference. Retrieved 2017-07-13. Enns, Gregory M.; Steiner, Robert D.; Cowan, Tina M. (2009 ...
GeneReviews/NCBI/NIH/UW entry on Alpha-Mannosidosis OMIM entries on Alpha-Mannosidosis ISMRD page on alpha-mannosidosis Hide ... Alpha-mannosidosis type 1 at NIH's Office of Rare Diseases Alpha-mannosidosis type 2 at NIH's Office of Rare Diseases. ... Alpha-mannosidosis is a lysosomal storage disorder caused by deficient activity of the enzyme alpha-D-mannosidase. In humans it ... The worldwide incidence of alpha-mannosidosis is in the range of 1 per 500,000 to 1 per 1,000,000. Mannosidosis is found in all ...
Alpha-ketoglutarate dehydrogenase deficiency Alpha-L-iduronidase deficiency Alpha-mannosidosis Alpha-sarcoglycanopathy Alpha- ... thalassemia Alpha thalassemia abnormal morphogenesis Alpha-thalassemia mental retardation syndrome Alport syndrome Alport ... Alpers disease Alpha 1-antitrypsin deficiency Alpha-2 deficient collagen disease ...
mannosidosis *Alpha-mannosidosis. *Beta-mannosidosis. *Sialidosis. *Schindler disease. Other. *solute carrier family (Salla ...
This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase), ... International Society for Mannosidosis & Related Diseases, ISMRD). Retrieved 2008-11-13. "Schindler Disease". National ... A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of ... Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency is a rare disease found in ...
... genetic types Mannosidosis Manouvrier syndrome Mansonelliasis Mantle cell lymphoma Marashi-Gorlin syndrome Marburg fever ... Male pseudohermaphroditism due to 17-beta-hydroxysteroid dehydrogenase deficiency Male pseudohermaphroditism due to 5-alpha- ...
Disruption of Golgi alpha-mannosidase II with swainsonine induces hybrid-type glycans. These glycans have a Man5GlcNAc2 core ... Castanospermine Mannosidosis Stegelmeier BL, Molyneux RJ, Elbein AD, James LF (May 1995). "The lesions of locoweed (Astragalus ... It is a potent inhibitor of Golgi alpha-mannosidase II, an immunomodulator, and a potential chemotherapy drug. As a toxin in ...
... not elsewhere classified Alpha-1-antitrypsin deficiency Bisalbuminaemia (E88.1) Lipodystrophy, not elsewhere classified (E88.2 ... Defects in glycoprotein degradation Aspartylglucosaminuria Fucosidosis Mannosidosis Sialidosis (mucolipidosis I) (E77.8) Other ... Testicular hypofunction 5-Alpha-reductase deficiency (with male pseudohermaphroditism) Testicular hypogonadism NOS (E30) ...
a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Malm D, Nilssen O (2008). "Alpha-mannosidosis". Orphanet J Rare Dis. ... a b c d e f g h Borgwardt L, Lund AM, Dali CI (2014). Alpha-mannosidosis - a review of genetic, clinical findings and options ... rarediseases.org/rare-diseases/alpha-mannosidosis/ *^ Guide to understanding mannosidosis. Society for Mucopolysaccharide ... "Alpha-mannosidosis" - news · newspapers · books · scholar · JSTOR (July 2008) (Learn how and when to remove this template ...
Check for Discount on Alpha-Mannosidosis Global Clinical Trials Review, H2, 2016 report by GlobalData. GlobalDatas clinical ... Alpha-Mannosidosis Therapeutics, Global, Clinical Trials and Average Enrollment by Top Countries, 2016* 6. Alpha-Mannosidosis ... Alpha-Mannosidosis Therapeutics Clinical Trials, North America, Top Countries, 2016* 9. Proportion of Alpha-Mannosidosis to ... Alpha-Mannosidosis Therapeutics, Global, Clinical Trials and Average Enrollment by Top Countries, 2016* 6. Alpha-Mannosidosis ...
Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Explore symptoms, ... medlineplus.gov/genetics/condition/alpha-mannosidosis/ Alpha-mannosidosis. ... Mutations in the MAN2B1 gene cause alpha-mannosidosis. This gene provides instructions for making the enzyme alpha-mannosidase ... Intracellular transport of human lysosomal alpha-mannosidase and alpha-mannosidosis-related mutants. Biochem J. 2004 Jul 15;381 ...
BMT Emerges as Leading Therapy for Treating Alpha Mannosidosis. Statistics show that alpha mannosidosis affects one in every 10 ... Alpha mannosidosis is an inherited medical condition tissues and organs of the human body to function in abnormal ways. The ... North America alpha mannosidosis market is also expected to witness a remarkable growth rate in the coming years. The orphan ... Alpha Mannosidosis Market Professional Survey Report 2017 Comprehensive Analysis and Market studies Research Report 2024. Press ...
Confirmed diagnosis of alpha-mannosidosis based on alpha mannosidase activity ,10% of normal in leukocytes or fibroblasts or ... Genetics Home Reference related topics: Alpha-mannosidosis Genetic and Rare Diseases Information Center resources: Alpha- ... Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis (SHAMAN). The safety ... alpha-Mannosidosis. Carbohydrate Metabolism, Inborn Errors. Metabolism, Inborn Errors. Genetic Diseases, Inborn. Lysosomal ...
Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected ... a-Mannosidosis (MIM 248500) is an autosomal recessive lysosomal storage disorder resulting from deficient activity of lysosomal ... Leu replacement at a position which is conserved among class 2 alpha-mannosidases from several species. ... alpha-mannosidase (LAMAN) (EC 3.2.1.24). The disease is characterized by massive intracellular accumulation of mannose-rich ...
... adolescents and children with mild to moderate forms of alpha-mannosidosis.. Alpha-mannosidosis is a rare inherited enzyme ... As alpha-mannosidosis is a very rare disease, the CHMPagreed that it is not possible to provide comprehensive data on the ... Because alpha-mannosidosis is a very rare disease, Lamzede was granted an orphan designation. As always at time of approval, ... The symptoms of alpha-mannosidosis range from mild to moderate and severe. Individuals with early onset severe and rapid ...
... and a patient pool with high disposable incomes will continue to keep North America at the forefront of the alpha mannosidosis ... Global Alpha Mannosidosis Market: Exclusivity Norms for Orphan Drugs in Europe and North America Ensure Sustainable Profits, ... Global Alpha Mannosidosis Market: Exclusivity Norms for Orphan Drugs in Europe and North America Ensure Sustainable Profits, ... Lamazym, an enzyme replacement therapy for treatment of alpha mannosidosis, is designated as an orphan drug in the U.S. and the ...
METHODS To study the genotype-phenotype relationship for alpha-mannosidosis 66 patients were included. Based on the predicted ... and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. ... leading to loss of lysosomal alpha-mannosidase activity. Symptoms include intellectual disabilities, hearing impairment, motor ... BACKGROUND Alpha-mannosidosis is caused by mutations in MAN2B1, ... alpha-Mannosidosis: functional cloning of the lysosomal alpha- ...
The goal of this study is to identify and validate a new biochemical marker for alpha-mannosidosis from the plasma of affected ... Mutations in the MAN2B1 gene cause alpha-mannosidosis. This gene provides instructions for making the enzyme alpha-mannosidase ... Alpha-mannosidosis is a rare lysosomal storage disorder of the Glycoprotein family of diseases and is closely related to ... Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Affected ...
... is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly ... Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. ... Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha- ... Alpha-mannosidosis is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive ...
alpha-Mannosidosis Mutation Database. A database on mutations, genotypes and the clinical and molecular aspects of alpha- ...
Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by a deficiency of alpha-mannosidase enzyme ... Demonstration of deficient alpha-mannosidase enzyme activity is considered the gold standard to confirm a diagnosis of alpha- ... This biochemical test is a quantitative measurement of alpha-mannosidase enzyme activity and can be used as a 1st tier test for ... patients with a clinical suspicion of alpha-mannosidosis. ... Alpha-mannosidosis : Alpha-mannosidase Enzyme Analysis. PRINT ...
What is Alpha-Mannosidosis? Compare Alpha-Mannosidosis symptoms Alpha-Mannosidosis treatments and . Share online in the health ... Learn about Alpha-Mannosidosis and other health conditions at HealtheTreatment. ... About Alpha-Mannosidosis. Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D- ... Alpha-mannosidosis is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly ...
Velmanase alfa for treating alpha-mannosidosis [ID800] In development [GID-HST10010] Expected publication date: TBC ...
Velmanase alfa for treating alpha-mannosidosis [ID800] In development [GID-HST10010] Expected publication date: 20 November ...
It is caused by mutations of the MAN2B1 gene, which lead to alpha-mannosidase deficiency. AM is associated with facial ... which may also be referred to as lysosomal acid hydrolase alpha-mannosidase or LAHAM. ... Alpha-mannosidosis (AM) is a lysosomal storage disease, ... Home Alpha-Mannosidosis Alpha-Mannosidosis Alpha-mannosidosis ... Alpha-Mannosidosis. Deficiency of Alpha-Mannosidase. Alpha-mannosidosis (AM) is a lysosomal storage disease, which may also be ...
... information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Alpha-mannosidosis ... Alpha-mannosidosis Title Other Names:. Lysosomal alpha-D-mannosidase deficiency; Alpha mannosidase B deficiency; Mannosidosis, ... Alpha mannosidosis is caused by a mutations. in the MAN2B1 gene. , which codifies a type of enzyme. (lysosomal alpha- ... 2014; http://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis. *Malm D & Nilssen O. Alpha-Mannosidosis. GeneReview. 2012; http ...
Mannosidosis. alpha-Mannosidosis. Mannosidase Deficiency Diseases. Mosses. Bryopsida. Bryophyta. Pneumocystis carinii. ...
Alpha mannosidosis. Gaucher Disease. Thalassemia major. Sickle cell disease (SCD). Diamond Blackfan Anemia (DBA). ... Alpha-mannosidosis Osteopetrosis Krabbe Disease Severe Combined Immunodeficiency Hemophagocytic Lymphohistiocytosis ...
beta-Mannosidosis: An inborn error of metabolism marked by a defect in the lysosomal isoform of BETA-MANNOSIDASE that results ... 10/08/1999 - "Glycoprotein lysosomal storage disorders: alpha- and beta-mannosidosis, fucosidosis and alpha-N- ... respectively alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency. ". ... alpha- and beta-mannosidosis, fucosidosis, aspartylglucosaminuria, and alpha-N-acetylgalactosaminidase deficiency (Schindler ...
GeneReviews/NCBI/NIH/UW entry on Alpha-Mannosidosis OMIM entries on Alpha-Mannosidosis alpha-Mannosidase at the US National ... alpha-Mannosidase (EC 3.2.1.24, alpha-D-mannosidase, p-nitrophenyl-alpha-mannosidase, alpha-D-mannopyranosidase, 1,2-alpha- ... exo-alpha-mannosidase) is an enzyme involved in the cleavage of the alpha form of mannose. Its systematic name is alpha-D- ... Malm D, Nilssen Ø (2008). "Alpha-mannosidosis". Orphanet J Rare Dis. 3: 21. doi:10.1186/1750-1172-3-21. PMC 2515294 . PMID ...
alpha-Mannosidosis 2018-03-23 Authorised Scenesse afamelanotide. Protoporphyria, Erythropoietic 2014-12-22 Authorised ...
alpha-Mannosidosis. Metabolic Diseases. Carbohydrate Metabolism, Inborn Errors. Metabolism, Inborn Errors. Genetic Diseases, ... Alpha-mannosidosis Mucopolysaccharidosis Type II Niemann-Pick Disease Niemann-Pick Disease Type A Neuronal Ceroid ... Alpha-mannosidosis Frontotemporal dementia with parkinsonism-17 Inclusion body myopathy with early-onset Paget disease and ... Alpha-Mannosidosis Sanfilippo Mucopolysaccharidoses Biological: DUOC-01 Phase 1 ...
3. Alpha-Mannosidosis. 4. Alport syndrome -- mental retardation -- midface hypoplasia -- elliptocytosis. 5. Angiofollicular ...
- In humans it is known to be caused by an autosomal recessive genetic mutation in the gene MAN2B1, located on chromosome 19, affecting the production of the enzyme alpha-D-mannosidase, resulting in its deficiency. (wikipedia.org)
- Alpha-mannosidosis is a lysosomal storage disorder , first described by Swedish physician Okerman in 1967. (wikipedia.org)
- A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars derived from glycoproteins in the lysosome , causes progressive lysosomal accumulation of mannose-rich oligosaccharides in all tissues, resulting in impaired cellular function and apoptosis (Figure 2). (wikipedia.org)
- Alpha-mannosidosis is a lysosomal storage disorder caused by deficient activity of the enzyme alpha-D-mannosidase. (wikipedia.org)
- Alpha-mannosidosis is a lifelong multi-systemic progressive disease, with neuromuscular and skeletal deterioration over decades. (wikipedia.org)
- Depending on the severity of the disease, alpha-mannosidosis has been classified into three proposed subtypes, based on severity and age of onset. (wikipedia.org)
- Generally, phenotypes of alpha-mannosidosis patients are not clearly distinguishable, which makes a prediction of the clinical course for an individual patient challenging. (wikipedia.org)
- A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars derived from glycoproteins in the lysosome, causes sugar build up and impairs cell function. (wikipedia.org)
- Patients may present to doctors, nurses or health visitors at different stages of progression, and with different ad hoc symptoms, making the link to suspect a diagnosis of alpha-mannosidosis difficult. (wikipedia.org)
- A milder form of alpha-mannosidosis involves mild to moderate intellectual disability which develops during childhood or adolescence. (wikipedia.org)
- A diagnosis is made by measuring the enzymatic activity of alpha-D-mannosidase in white blood cells. (wikipedia.org)