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

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

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.

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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
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

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2020

Do you have updated information on this disease? We want to hear from you.

Treatment Treatment

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

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

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 Genetics Home Reference.

Related Diseases Related Diseases

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

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

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

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
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/

Do you know of an organization? We want to hear from you.

Learn More 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.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

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.

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Have a question? Contact a GARD Information Specialist.

References References

Alpha-Mannosidosis. Genetics Home Reference. 2014; http://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis.
Malm D & Nilssen O. Alpha-Mannosidosis. GeneReview. 2012; http://www.ncbi.nlm.nih.gov/books/NBK1396/.
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.
Kniffen CL. Mannosidosis, Alpha B, Lysosomal. OMIM. May 24 2016; http://omim.org/entry/248500.