alpha-mannosidosis

What is Alpha-Mannosidosis?

Alpha-mannosidosis is a disease that causes the body to be unable to break down a specific type of sugar called mannose. This results in organ and tissue damage. Harmful genetic changes (variants) in the MAN2B1 gene cause this disease.

Most individuals with alpha-mannosidosis have speech delays and learning difficulties (intellectual disability). They often experience a lack of muscle coordination and balance (ataxia) and general muscle weakness (myopathy). As a result, they may learn to walk more slowly than other children and appear clumsy. Hearing loss and frequent infections (immunodeficiency) are also common symptoms. Many individuals have differences in the shape of some of their bones.

Some individuals with the disease experience psychiatric problems, often beginning in late puberty or early adolescence. These psychiatric issues have included depression, confusion, anxiety, and hallucinations. Other features include unique facial characteristics, bone and joint problems, a buildup of fluid around the brain (hydrocephaly), and vision problems.

Alpha-mannosidosis can range from mild to severe.

Mild form (type 1)

The mildest form, type 1, appears after the age of ten. Individuals with type 1 typically do not have skeletal abnormalities but do have muscle weakness.

Moderate form (type 2)

In the moderate form, symptoms appear before the age of ten. This form of the disease causes skeletal abnormalities and muscle weakness.

Severe form (type 3)

In the severe form, signs and symptoms appear in early infancy. In this form of the disease, individuals have severe nervous system (neurological) symptoms and typically do not survive past infancy or childhood.

How common is Alpha-Mannosidosis?

The incidence of alpha-mannosidosis in the population is between 1 in 500,000 to 1,000,000.

How is Alpha-Mannosidosis treated?

There is no cure for alpha-mannosidosis. However, enzyme replacement therapy (ERT) using velmanase alfa is considered the standard treatment for the condition. ERT has led to improved clinical symptoms. Individuals with the severe form may also undergo a hematopoietic stem cell transplantation (HSCT). Other supportive treatments for alpha-mannosidosis focus on preventing complications and improving an individual's quality of life.

Depending on the individual, treatments may include antibiotics to reduce bacterial infections, hearing aids and/or tubes to drain fluid from the middle ear, physical therapy to aid in movement, speech therapy and special-education classes to improve learning and speech, the use of wheelchairs and other aids to assist with mobility, glasses to correct vision problems, and the placement of an implanted shunt near the brain to help drain extra fluid.

What is the prognosis for an individual with Alpha-Mannosidosis?

Individuals with the mild form of alpha-mannosidosis typically live into adulthood, with many surviving into their fifties or sixties. For these individuals, the disease normally progresses slowly. Frequent infections are most common in childhood and can improve with age. Other symptoms, such as psychiatric diseases, bone disease, and ataxia, may be more common as individuals get older.

Those with the most severe form of alpha-mannosidosis experience rapid progression of symptoms and often die before birth or in childhood, usually from severe neurological complications or infection. The prognosis of the condition may improve over time as more individuals are treated with ERT.