Alpha-mannosidosis is a rare inherited disorder that affects organs and tissues of the body. This may cause an intellectual disability, distinguishing facial features, and skeletal abnormalities in an individual. Characteristic facial features can include a large head, low hairline, large ears, and rounded eyebrows, protruding jaw, flattened bridge of the nose, overgrown gums, widely spaced teeth, and large tongue. The skeletal abnormalities caused by alpha-mannosidosis disorder include thickening of the bones at the top of the skull (calvaria), reduced bone density (osteopenia), deformations of the spinal bones (vertebrae), weakening of the bones and joints and bowed legs or knock knees. Some individuals may also experience ataxia i.e. difficulty in movement co-ordination, myopathy i.e. muscle weakness; poor development of motor skills such as speech impairments; sitting and walking; enlargement of the liver and spleen, increased risk of infections; a buildup of fluid in the brain also known as hydrocephalus; hearing loss; and cataract. In some cases psychiatric symptoms are also observed which include depression, hallucinations, or anxiety.
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Individuals suffering from alpha-mannosidosis disorder may experience signs and symptoms which can range from mild to severe. The onset of this disorder in infants occurs with severe neurological deterioration coupled with rapid progression. In such cases, the chances of survival for the individual past childhood are very low. Moreover, an affected fetus may die before birth in the most severe cases. Few individuals with alpha-mannosidosis may experience milder signs and symptoms that are known to appear later and progress more slowly. Individuals with later-onset of alpha-mannosidosis are known to survive into their fifties. Laboratory testing is required for detection of even the mildest cases.
A diagnosis is made by measuring the enzymatic activity of alpha-D-mannosidase in white blood cells. Diagnosis of alpha mannosidosis is based on the levels of the enzyme. Decreased level of the enzyme in comparison to standard levels, results into positive diagnosis of the disorder. However, late diagnosis in the disease’s progression, in cases of mild symptoms, or the biochemical diagnosis does not yield conclusive results may result into under diagnosis of the disorder.
Currently, the only way to treat the underlying cause of alpha-mannosidosis, is to treat the symptoms as recommended by physicians in order to avoid complications and thus helping to enhance the individuals quality of life. Based on the person’s symptoms, a range of treatments often recommended by physicians include antibiotics to treat viral infections; tubes to drain fluid from the middle ear; hearing aids; speech therapy; physical therapy to aid in movement; education classes to facilitate learning; use of orthopedic aids and may also require implantation of shunt near the brain to help drain fluid buildup. Specific treatments for mannosidosis include hematopoietic stem cell transplantation and enzyme replacement therapy. Moreover, extensive research is being carried out that may result into other possible treatments.
Incidences of alpha-mannosidosis are known to occur in 1 per 500,000 to 1 per 1,000,000 across the world. Mannosidosis is found in all races in Europe, Africa, North America, and Asia. A number of clinical trials are being conducted currently and are under assessment by monotherapy products, combination products, route of administration and molecule type. Some of the key players contributing to the global alpha mannosidosis market include Zymenex A/S, and Cytomedix, Inc. Some investigations are also being carried out by universities and institutions such as Masonic Cancer Center, The Royal Children’s Hospital and University of Louisville.
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