Alpha-mannosidosis- type 2


Alpha-mannosidosis adult-onset form


Alpha mannosidosis type 2 is a lysosomal storage disorder and it is rare inherited metabolic disorder involving a deficiency of an enzyme (alpha-mannosidosase) which results in the accumulation of certain chemicals in the body which leads to progressive damage. This form of the condition is less severe than type I (infantile form). Signs and symptoms develop as a result of the toxic build-up of sugars (i.e., mannose-containing oligosaccharides) in the cells of the body. People with this disorder tend to develop bone abnormalities and muscle weakness by age 10.


Signs and symptoms vary, but often include mild to moderate intellectual disability, hearing loss, weakened immune system, distinctive facial features, and cerebellar disorders (e.g., ataxia). Symptoms slowly worsen over time. 

More common signs and symptoms of alpha mannosidosis type 2 include:

  • Bone abnormalities
  • Muscle weakness
  • Intellectual disability
  • Developmental delays (e.g., motor and speech)
  • Hearing loss
  • Weakened immune system
  • Cerebellar disorders (e.g., ataxia)
  • Occasional psychiatric symptoms (e.g., depression, anxiety, or hallucinations)
  • Cataract
  • Enlarged liver and spleen (with normal function)
  • Arthritis

People with alpha-mannosidosis type 2 often have distinct facial features, including large head size, large forehead, low hair line, rounded eyebrows, large ears, wide spaced teeth, overgrown gums, large tongue, protruding jaw, and flattened bridge of the nose.


Other Symptoms:

  • Progressive neurological degeneration
  • Mental retardation
  • Sensorineural deafness
  • Reduced plasma level of mannosidase
  • Reduced level of mannosidase in white blood cells
  • Frequent respiratory infection
  • Loss of previously acquired psychomotor skills
  • Coarse facial features
  • Thick eyebrows
  • Widely spaced front teeth
  • Protruding jaw
  • Low frontal hairline
  • Fecal incontinence
  • Brain atrophy
  • Dysostosis
  • Skeletal abnormalities
  • Dysmorphic face
  • Corneal opacities
  • Enlarged liver
  • Hernia
  • Polyarthropathy


This disorder is caused by a mutation in MAN2B1 and is inherited in an autosomal recessive fashion.


There is limited information regarding long-term outlook for people with alpha mannosidosis. Much of the literature describes cases in children. Frequency of infections, such as colds, pneumonia, ear infection, and stomach flu is often worse in early childhood and improves with age. Muscle weakness and central nervous system disease (e.g., cerebellar disorders) tend to become evident in adolescence to early adulthood. These symptoms tend to slowly worsen overtime. Intellectual disability is common and adults tend to have an IQ of 60-80. Intellectual disability remained stable in some, but not all reported cases. Bone involvement is highly variable, but symptoms may decrease with age. While people with alpha mannosidosis have lived well into adulthood, there is very limited data regarding life expectancy and cause of death in affected adults.


There is no cure for Alpha-Mannosidosis. Treatment is limited to reducing or controlling the symptoms of this disorder.

Current treatment options for alpha mannosidosis may include bone marrow transplant or peripheral blood stem cell transplantation. Enzyme replacement therapy may be an additional treatment option in the future.

Treatments to address individual symptoms are recommended as needed, such as vaccinations, antibiotics, hearing aids, glasses, orthopedic and other assistive devices, educational interventions, and speech therapy. Regular follow-up to monitor health and treatment response is advised.


  • NIH