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Disease Profile


Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset






Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Lysosomal alpha-D-mannosidase deficiency; Alpha mannosidase B deficiency; Mannosidosis, alpha B lysosomal


Congenital and Genetic Diseases; Eye diseases; Heart Diseases;


Alpha mannosidosis  is a lysosomal storage disorder, a form of inborn metabolic disease. It is characterized by intellectual disability, hearing loss, ataxia, skeletal abnormalities, and coarse facial features.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.

According to the severity of the symptoms it is classified in 3 sub-types:

  • Type 1: A mild form recognized after age ten years with absence of skeletal abnormalities, muscle problems (myopathy), and slow progression
  • Type 2: A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression. It is the most common form.
  • Type 3: A severe form manifested as pregnancy loss or early death from progressive central nervous system involvement.

Alpha mannosidosis is caused by a mutations in the MAN2B1 gene which codifies a type of enzyme (lysosomal alpha-mannosidase), that degrade glycoproteins (proteins attached to sugar residues) into smaller fragments. The lack or deficiency of this enzyme results in the toxic build-up of sugars (i.e., mannose-containing oligosaccharides) in the cells of the body.[1][2] Inheritance is autosomal recessive. Treatment aims to avoid complications and improve the quality of life. Ongoing research for new treatments include bone marrow transplant and enzyme replacement.[2][3]


Signs and symptoms varies among the affected people. In general, affected individuals may have intellectual disability, distinctive facial features, and skeletal abnormalities. At least three clinical types (mild, moderate, and severe) have been suggested according to the severity of the symptoms:[2]

  • Type 1. Mild form with onset after age ten years, with muscle weakness (myopathy), slow progression, and absence of skeletal abnormalities
  • Type 2. Moderate form with onset before age ten years, with myopathy, slow progression, and presence of 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. Most cases are classified into this type.
  • Type 3. Severe form with progressive symptoms, leading to early death from primary central nervous system (brain and spinal cord) involvement or infection

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.

Other symptoms may include:[1][2]

  • Difficulty in coordinating movements (ataxia)
  • Delay in developing motor skills such as sitting and walking
  • Speech impairments
  • Increased risk of infections due to immunodeficiency (with decreased ability to produce specific substances to fight infections (antibodies)
  • Enlargement of the liver and spleen (hepatosplenomegaly)
  • Buildup of fluid in the brain (hydrocephalus)
  • Hearing loss
  • Eye problems, such as clouding of the lens of the eye (cataract), and near-sightednes (myopia)
  • Pain and inflamed joints

Some people with alpha-mannosidosis have mental problems such as depression, anxiety, or hallucinations. Heart and kidney problems may also occur.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.


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.[2]

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.[2][3]

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Clouding of the lens of the eye
    Cloudy lens

    [ more ]

    Coarse facial features
    Coarse facial appearance
    Corneal opacity
    Craniofacial hyperostosis
    Excessive bone growth of the skull and face
    Delayed skeletal maturation
    Delayed bone maturation
    Delayed skeletal development

    [ more ]

    Depressed nasal bridge
    Depressed bridge of nose
    Flat bridge of nose
    Flat nasal bridge
    Flat, nasal bridge
    Flattened nasal bridge
    Low nasal bridge
    Low nasal root

    [ more ]

    Global developmental delay
    Hearing impairment
    Hearing defect

    [ more ]

    Enlarged liver
    Hypoplastic inferior ilia
    Intellectual disability
    Mental deficiency
    Mental retardation
    Mental retardation, nonspecific

    [ more ]

    Abnormally large tongue
    Increased size of tongue
    Large tongue

    [ more ]

    Skeletal dysplasia
    Increased spleen size
    Type II diabetes mellitus
    Noninsulin-dependent diabetes
    Type 2 diabetes
    Type II diabetes

    [ more ]

    30%-79% of people have these symptoms
    Abnormality of the helix
    Bowing of the long bones
    Bowed long bones
    Bowing of long bones

    [ more ]

    Chronic otitis media
    Chronic infections of the middle ear
    Generalized abnormality of skin
    Generalised abnormality of skin
    Gingival overgrowth
    Gum enlargement
    Hip dysplasia
    Wide-set eyes
    Widely spaced eyes

    [ more ]

    Inguinal hernia
    Hunched back
    Round back

    [ more ]

    Large ears
    Muscular hypotonia
    Low or weak muscle tone
    Narrow palate
    Narrow roof of mouth
    Open bite
    Absence of overlap of upper and lower teeth
    Open bite between upper and lower teeth

    [ more ]

    Prominent supraorbital ridges
    Prominent brow
    Short neck
    Decreased length of neck
    5%-29% of people have these symptoms
    Joint inflammation
    Avascular necrosis
    Death of bone due to decreased blood supply
    Dental malocclusion
    Bad bite
    Malalignment of upper and lower dental arches
    Misalignment of upper and lower dental arches

    [ more ]

    Sensory hallucination

    [ more ]

    Increased intracranial pressure
    Rise in pressure inside skull
    Increased size of skull
    Large head
    Large head circumference

    [ more ]

    Mandibular prognathia
    Big lower jaw
    Increased projection of lower jaw
    Increased size of lower jaw
    Large lower jaw
    Prominent chin
    Prominent lower jaw

    [ more ]

    Recurrent respiratory infections
    Frequent respiratory infections
    Multiple respiratory infections
    respiratory infections, recurrent
    Susceptibility to respiratory infections

    [ more ]

    Synostosis of joints
    Fusion of joints
    Conditions with similar signs and symptoms from Orphanet
    The principle differential diagnoses are other lysosomal storage diseases, such as the various forms of mucopolysaccharidosis (see these terms).
    Visit the Orphanet disease page for more information.


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Alpha-mannosidosis. Click on the link to view a sample search on this topic.


          1. Alpha-Mannosidosis. Genetics Home Reference. 2014; https://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis.
          2. Malm D & Nilssen O. Alpha-Mannosidosis. GeneReview. 2012; https://www.ncbi.nlm.nih.gov/books/NBK1396/.
          3. Borgwardt L, Lund AM & Dali CI. Alpha-mannosidosis a review of genetic, clinical findings and options of treatment.. Pediatr Endocrinol Rev. September, 2014; 12(1):185-91. https://www.ncbi.nlm.nih.gov/pubmed/25345101.
          4. Kniffen CL. Mannosidosis, Alpha B, Lysosomal. OMIM. May 24 2016; https://omim.org/entry/248500.

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