A type of lysosomal storage disease that is often caused by a deficiency of alpha-D-mannosidase resulting in the accumulation of mannose-rich oligosaccharides in cells and tissues
Lysosomal storage disease is a collective term for the various metabolic disorders due to defects in lysosomal function resulting in an abnormal accumulation of toxic materials in the cell. One of them is alpha-mannosidosis. In humans, this condition is caused by pathological mutations in the gene MAN2B1. The gene is located on chromosome 19. It codes for the enzyme alpha-D-mannosidase. This enzyme is responsible for the breakdown of complex sugars (oligosaccharides) attached to glycoproteins. Deficiency of this enzyme or a dysfunctional form of this enzyme disrupts its activity. As a result, mannose-rich oligosaccharides accumulate in the lysosomes. Buildup of these molecules impairs cellular function and could end up in apoptosis.
Alpha-mannosidosis may be classified based on the age of onset: type 1, type 2, and type 3. Type 1 alpha-mannosidosis has the mildest symptoms, manifesting after ten years of age. Type 2 is the moderate form with symptoms (e.g. myopathy and skeletal deformities) manifesting often before reaching the age of ten. Type 3 is the severe form and potentially fatal at early childhood especially when the central nervous system is affected.
Alpha-mannosidosis is hereditary; it is inherited in an autosomal recessive pattern.