Disease relevance of alpha-Mannosidosis

• Cells affected with alpha-mannosidosis stained with Concanavalia ensiformis (Con A), Triticum vulgaris (WGA), and succinyl-WGA (S-WGA), while beta-mannosidosis cells did not stain with any of the lectins used [1].

High impact information on alpha-Mannosidosis

• Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency [2].
• alpha-Mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal alpha-mannosidase (LAMAN) [3].
• In cats with alpha-mannosidosis induced by swainsonine, some pyramidal neurons showed GM2-like immunoreactivity after 4 weeks of treatment, whereas ectopic dendrites only became evident after 7 weeks of treatment [4].
• Here we report on the correction of storage in a mouse model of alpha-mannosidosis after intravenous administration of lysosomal acid alpha-mannosidase (LAMAN) from bovine kidney, and human and mouse recombinant LAMAN [5].
• It also hydrolyzes (Man)2-GlcNAc from the urine of an alpha-mannosidosis patient, 1,4-D-mannobiose and mannotriose isolated from ivory nut mannan, 4-O-beta-D-mannopyranosyl-L-rhamnose, 6-O-beta-D-mannopyranosyl-D-galactose and 4-O-beta-D-mannopyranosyl-N-acetylglucosamine [6].

Chemical compound and disease context of alpha-Mannosidosis

• The specificity of human liver lysosomal alpha-mannosidase (EC 3.2.1.24) towards a series of oligosaccharide substrates derived from high-mannose, complex and hybrid asparagine-linked glycans and from the storage products in alpha-mannosidosis was investigated [7].
• The degradation of oligosaccharides derived from dolichol intermediates by ER/cytosolic mannosidase now explains why cats and cattle with alpha-mannosidosis store and excrete some unexpected oligosaccharides containing only one GlcNAc residue [8].
• Alpha-mannosidosis is a lysosomal storage disorder characterised by the lysosomal accumulation of mannose-containing oligosaccharides and a range of pathological consequences, caused by a deficiency of the lysosomal enzyme alpha-mannosidase [9].

Anatomical context of alpha-Mannosidosis

• An experimentally induced and reversible model of a neuronal storage disease, swainsonine-induced feline alpha-mannosidosis, has been used to study the modifiability of ectopic, axon hillock-associated neurites and their new synaptic contacts [10].

Gene context of alpha-Mannosidosis

• Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis [11].
• Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis [12].
• In humans, cattle, cat and guinea pig, lack of lysosomal alpha-mannosidase activity causes the autosomal recessive disease alpha-mannosidosis [13].
• Lack of LAMAN activity leads to the lysosomal storage disorder alpha-mannosidosis (MIM No. 248500) [14].
• Effective treatment of alpha-mannosidosis by allogeneic hematopoietic stem cell transplantation [15].

References