Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Affected individuals may have intellectual disability, distinctive facial features, and skeletal abnormalities. Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Characteristic facial features can include a large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The skeletal abnormalities that can occur in this disorder include reduced bone density (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and joints.
Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocephalus); hearing loss; and a clouding of the lens of the eye (cataract). Some people with alpha-mannosidosis experience psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric disturbance may be triggered by stressors such as having undergone surgery, emotional upset, or changes in routine.
- Mild liver and spleen enlargement
- Large head
- Large ears
- Enlarged tongue
- Flat nos
- Low hairline
- Coarse facial features
- Lumbar gibbus
- Widely spaced teeth
- eReduced muscle tone
- Big feet
- Big hands
- Bowed femoral bone
- Hypertrophy of gingivaDysostosis multiplex
- Projecting jaw
- Tall stature
- Immunoglobulin deficiency
- Recurring respiratory tract infections
- Immunological impairment
- Mental retardation
Mutations in the MAN2B1 gene cause alpha-mannosidosis. This gene provides instructions for making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are compartments that digest and recycle materials in the cell. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides containing a sugar molecule called mannose.
Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides accumulate in the lysosomes and cause cells to malfunction and eventually die. Tissues and organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell death, leading to the characteristic features of alpha-mannosidosis.
The diagnosis of alpha-mannosidosis relies on demonstration of deficient acid alpha-mannosidase enzyme activity in peripheral blood leukocytes or other nucleated cells such as fibroblasts. Carrier testing by this method is unreliable because of overlap of enzyme activity between carriers and non-carriers. MAN2B1 is the only gene known to be associated with alpha-mannosidosis. Sequence analysis is available on a clinical basis.
There is no cure for Alpha-Mannosidosis. Treatment is limited to reducing or controlling the symptoms of this disorder.
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