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Alpha-mannosidosis


Title




Other Names:
Lysosomal alpha-D-mannosidase deficiency; Alpha mannosidase B deficiency; Mannosidosis, alpha B lysosomal
Categories:
Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Metabolic disorders; Musculoskeletal Diseases; Nervous System Diseases See More

Summary Summary


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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]
Last updated: 2/20/2017

Symptoms Symptoms


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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]

Last updated: 2/20/2017

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.

Showing of 80 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ]
0000518
Coarse facial features
Coarse facial appearance
0000280
Corneal opacity 0007957
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ]
0002750
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 ]
0005280
Global developmental delay 0001263
Hearing impairment
Deafness
Hearing defect
[ more ]
0000365
Hepatomegaly
Enlarged liver
0002240
Hypoplastic inferior ilia 0008821
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ]
0001249
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ]
0000158
Skeletal dysplasia 0002652
Splenomegaly
Increased spleen size
0001744
Type II diabetes mellitus
Noninsulin-dependent diabetes
Type 2 diabetes
Type II diabetes
[ more ]
0005978
30%-79% of people have these symptoms
Abnormality of the helix 0011039
Bowing of the long bones
Bowed long bones
Bowing of long bones
[ more ]
0006487
Chronic otitis media
Chronic infections of the middle ear
0000389
Generalized abnormality of skin
Generalised abnormality of skin
0011354
Gingival overgrowth
Gum enlargement
0000212
Hip dysplasia 0001385
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ]
0000316
Inguinal hernia 0000023
Kyphosis
Hunched back
Round back
[ more ]
0002808
Macrotia
Large ears
0000400
Muscular hypotonia
Low or weak muscle tone
0001252
Narrow palate
Narrow roof of mouth
0000189
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth
[ more ]
0010807
Prominent supraorbital ridges
Prominent brow
0000336
Scoliosis 0002650
Short neck
Decreased length of neck
0000470
5%-29% of people have these symptoms
Arthritis
Joint inflammation
0001369
Avascular necrosis
Death of bone due to decreased blood supply
0010885
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ]
0000689
Hallucinations
Hallucination
Sensory hallucination
[ more ]
0000738
Increased intracranial pressure
Rise in pressure inside skull
0002516
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ]
0000256
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ]
0000303
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ]
0002205
Synostosis of joints
Fusion of joints
0100240
Widely spaced teeth
Wide-spaced teeth
Widely-spaced teeth
[ more ]
0000687
Percent of people who have these symptoms is not available through HPO
Abnormal rib cage morphology
Abnormality of the rib cage
0001547
Autosomal recessive inheritance 0000007
Babinski sign 0003487
Broad forehead
Increased width of the forehead
Wide forehead
[ more ]
0000337
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Decreased circulating antibody level 0004313
Delayed myelination 0012448
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ]
0000457
Dysarthria
Difficulty articulating speech
0001260
Dysostosis multiplex 0000943
Epicanthus
Eye folds
Prominent eye folds
[ more ]
0000286
Femoral bowing
Bowed thighbone
0002980
Flat occiput 0005469
Frontal bossing 0002007
Gait ataxia
Inability to coordinate movements when walking
0002066
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ]
0001290
Gliosis 0002171
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ]
0001510
Hyperreflexia
Increased reflexes
0001347
Hypertrichosis 0000998
Impaired smooth pursuit 0007772
Increased vertebral height 0004570
Limb ataxia 0002070
Low anterior hairline
Low frontal hairline
Low-set frontal hairline
[ more ]
0000294
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ]
0011800
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pectus carinatum
Pigeon chest
0000768
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections
[ more ]
0002718
Retinal degeneration
Retina degeneration
0000546
Sensorineural hearing impairment 0000407
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Spinocerebellar tract disease in lower limbs 0007232
Spondylolisthesis
Displacement of one backbone compared to another
Slipped backbone
[ more ]
0003302
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows
[ more ]
0000574
Thickened calvaria
Increased thickness of skull cap
Thickened skull cap
[ more ]
0002684
Thoracolumbar kyphosis 0005619
Vacuolated lymphocytes 0001922
Showing of 80 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 2/1/2021
Do you have updated information on this disease? We want to hear from you.

Treatment Treatment


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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]
Last updated: 2/20/2017

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.

Prognosis Prognosis


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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.[2][4]
Last updated: 2/20/2017

Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases


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Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

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.

Research Research


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Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations Organizations


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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

  • Canadian Society for Mucopolysaccharide and Related Diseases Inc. (Canadian MPS Society)
    #218-2055 Commercial Drive
    Vancouver, BC V5N OC7
    Canada
    Toll-free: 800-667-1846
    Telephone: 604-924-5130
    Fax: 604-924-5131
    E-mail: info@mpssociety.ca
    Website: http://www.mpssociety.ca
  • Hide and Seek Foundation for Lysosomal Storage Disease Research
    6475 East Pacific Coast Highway
    Suite 466
    Long Beach, CA 90803
    Toll-free: (844) 762-7672
    E-mail: info@hideandseek.org
    Website: https://hideandseek.org
  • National MPS Society
    P.O. Box 14686
    Durham, NC 27709-4686
    Toll-free: 1-877-MPS-1001 (1-877-677-1001)
    Telephone: +1-919-806-0101
    Fax: +1-919-806-2055
    E-mail: info@mpssociety.org
    Website: https://mpssociety.org/
  • Society for Mucopolysaccharide (MPS) Diseases
    MPS House Repton Place White Lion Road
    Amersham Buckinghamshire
    HP7 9LP
    United Kingdom
    Telephone: (+44) 0345 389 9901
    E-mail: mps@mpssociety.co.uk
    Website: http://www.mpssociety.co.uk
  • The International Advocates for Glycoprotein Storage Diseases (ISMRD)
    20880 Canyon View Drive
    Saratoga, CA 95070
    E-mail: info@ismrd.org
    Website: https://www.ismrd.org/

Organizations Providing General Support

  • Alex The Leukodystrophy Charity (Alex TLC)
    45 Peckham High Street
    London, SE15 5EB United Kingdom
    Telephone: 020 7701 4388
    E-mail: info@alextlc.org
    Website: https://www.alextlc.org
Do you know of an organization? We want to hear from you.

Learn More Learn More


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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.

News & Events News & Events


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News

  • Rare Disease Day at NIH 2021
    March 1, 2021

Other Conferences

  • 2012 International Conference for Glycoprotein Storage Diseases, July 27, 2012 - July 30, 2012
    Location: Crowne Plaza Hotel, Charleston, SC
    Description: The International Society for Mannosidosis & Related Storage Diseases (ISMRD) is sponsoring the 2012 International Conference for Glycoprotein Storage Diseases. The Scientific/Family meetings will be held concurrently on July 28th and 29th. Alongside this meeting, they are hosting the extension of the Natural History Study, with clinic days on July 27th and 30th.

GARD Answers GARD Answers


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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References


  1. Alpha-Mannosidosis. Genetics Home Reference. 2014; http://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis.
  2. Malm D & Nilssen O. Alpha-Mannosidosis. GeneReview. 2012; http://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; http://omim.org/entry/248500.
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