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What is alpha-mannosidosis?

Alpha-mannosidosis is an ultra-rare, inherited condition known as a lysosomal storage disorder that causes a range of symptoms. It occurs when the body is unable to make an enzyme that breaks down certain glycoproteins, which are a type of sugar, in cells. This causes the sugars to build up in part of the cell called a lysosome, which can damage organs and tissues throughout the body.

a rare disease
affecting about
1 in 500,000-
live births

a hereditary

All forms are progressive,
independent of severity

Symptoms may first
become evident in infancy
or later in adolescence

What causes alpha-mannosidosis?

Alpha-mannosidosis is caused by hereditary mutations in a gene called MAN2B1.

What is a hereditary mutation?

Hereditary mutations are inherited from one’s father or mother, or in the case of alpha-mannosidosis, from both parents.

What is MAN2B1?

The gene MAN2B1 contains the information to make the enzyme α-mannosidase, which normally helps to break down complex sugars called oligosaccharides. Oligosaccharides are used to build bones, cartilage, skin, tendons, and many other tissues in the body.

What happens when α-mannosidase is not working properly?

A defect in the activity of α-mannosidase means that an individual is not able to correctly recycle old oligosaccharides. Due to this, partially broken-down mannose-containing chemicals remain stored in the body and begin to build up over time. This causes progressive damage to cells. Infants may show only a few signs of the disease, but as the disease progresses, symptoms start to appear.

What are the symptoms of alpha-mannosidosis?

Symptoms of alpha-mannosidosis include:

  • Hydrocephalus (fluid build-up in the brain)
  • Recurrent infections
  • Immune deficiency
  • Hearing loss
  • Skeletal abnormalities (such as scoliosis, which is a curvature of the spine)
  • Cognitive impairment
  • Coarse facial features
  • Disturbed motor function (such as muscle weakness and joint abnormalities, which may appear as clumsiness)
  • Developmental delay

Symptoms can vary greatly from person to person and may change as patients get older.

Alpha-mannosidosis is a progressive disease, meaning symptoms will get worse over time as disease progresses.


  • Hearing loss
  • Delayed speech, motor, or mental functions
  • Fluid build-up in the brain in the first year of life

2nd to 3rd decade of life

  • Muscular weakness
  • Ataxia (problems with coordination or balance)
  • Skeletal abnormalities
  • Joint problems
  • Psychiatric symptoms


  • Inability to achieve social independence
  • Life expectancy unknown, although living to over 50 years old is not uncommon