Alpha Mannosidosis

From WikiGenetics

1 Name of Condition
2 Definition
3 Description, Signs and Symptoms
4 Inheritance
5 Demographics
6 Diagnosis
7 Treatment and Management
8 Prognosis
9 Resources
10 References

[edit] Name of Condition

Alpha Mannosidosis

[edit] Definition

Alpha Mannosidosis is a rare inherited disorder that causes mental retardation, distinctive facial and physical features, and is typically fatal during childhood or even earlier, although people with late-onset forms of the condition may survive well into adulthood.

[edit] Description, Signs and Symptoms

Signs and symptoms of alpha-mannosidosis include mental retardation; distinctive facial features; and skeletal abnormalities such as 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. Characteristic facial features 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.

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; a clouding of the lens of the eye (cataract); and psychiatric symptoms such as depression, anxiety, or hallucinations.

Signs of alpha-mannosidosis may appear in infancy with rapid progression and severe neurological deterioration. Early-onset alpha-mannosidosis is typically fatal during childhood. In the most severe cases, an affected fetus may die before birth.

Some individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The mildest cases may be detected only through laboratory testing and result in few if any symptoms.

(http://ghr.nlm.nih.gov)

[edit] Inheritance

Alpha Mannosidosis is inherited through an autosomal recessive pattern. The condition is cause by a mutation in the MAN2B1 gene, located on chromosome 8. The MAN2B1 gene provides instructions for making the enzyme alpha-mannosidase. Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down sugars, which then accumulate in the cells, causing cells to malfunction and eventually die.

[edit] Demographics

Alpha Mannosidosis affects approximately 1 in 500,000 people. It is usually present from birth, although some forms do not show symptoms until later in life. The severity of the case also determines life expectancy, although in most cases mortality occurs in childhood.

[edit] Diagnosis

Alpha Mannosidosis may be suspected in individuals with characteristic mental retardation and physical features, and blood and urine tests that show high oligosaccharide content would be suggestive of the disorder as well. A genetic test for the MAN2B1 gene would prove diagnostic, and could be useful to detect carriers for relatives of the affected individual to determine their risk for having the condition as well.

[edit] Treatment and Management

Symptoms may be treated in many different ways, including treating bacterial and viral infections which may occur due to immunodeficiency, hearing aids or glasses for those with hearing or vision loss, and use of physical therapy or a wheelchair for increased mobility. Educational resources such as speech therapy or sign language may also be appropriate depending on the person. Affected individuals should have their health closely monitored by a doctor through frequent checkups.

Some therapies which are being investigated are bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), enzyme replacement therapy (ERT), and gene therapy. BMT has shown some helpfulness in a few studies, but is not widely used. PBSCT is also rarely used, but in recent studies has shown good benefits for the recipient of the treatment including increased enzyme activity and decreased skeletal dysplasia. ERT has shown promise in animal trials but so far has not been tested on humans, and gene therapy is also only in research stages of development.

[edit] Prognosis

For severe cases and cases where the condition is evident from birth, life expectancy is low, and mortality often occurs during childhood. In late-onset cases, adults may survive into their 50s and occasionally be relatively symptom-free.