Alpha-Mannosidosis is caused by deficient activity of the enzyme alpha-D-mannosidase. There are three clinical subtypes, which include
- – a mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1)
- – a moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2)
- – a severe form manifested as prenatal loss or early death from progressive central nervous system involvement (type 3)
Symptoms range widely in their onset and severity. Often the appearance of an affected individual includes the following: Intellectual disability; distinctive facial features; and 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. Characteristic facial features 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.
Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocephalus); hearing loss; a clouding of the lens of the eye (cataract); and psychiatric symptoms such as depression, anxiety, or hallucinations. (The paper on psychiatric symptoms is reprinted with permission of the author and the Journal of Intellectual Disability Reserach.)
Alpha-Mannosidosis is believed to occur in approximately 1 in 500,000 people worldwide
- Bone marrow/ stem cell transplant: There have been a number of children who have had this treatment and their stories can be found on our website under Family Stories. Just a few dozen transplants have been done worldwide and long term data is needed to confirm the value of this treatment. However; despite the risks, family and some clinical reports indicate good responses in many cases where the transplant is done early in life
- Enzyme replacement therapy has been developed by Zymenex then subsequently by Chiesi an Italian Pharmaceutical company. This therapy has completed its clinical trial phases and in early 2018 is going through the European regulatory and reimbursement applications process.
Medical and Research Information
- • Genetics Home Reference:has a short summary description of Alpha-Mannosidosis.
- • GeneReviews: This GeneReviews article contains the most comprehensive and detailed description of Alpha-Mannosidosis, written for health professionals but not too difficult for lay readers to understand. Access is free to all users.
- • Orphanet: A database dedicated to information on rare diseases and orphan drugs. Access is free of charge.
- • Clinical Trials: A registry of federally and privately supported clinical trials conducted in the United States and around the world. This site gives you information about the trial’s purpose and who may participate and the locations.
- • PubMed: Provides the latest research and other published papers on Alpha-Mannosidosis.•
- • OMIM: Technical information about the genetics of Alpha-Mannosidosis. OPMIM is a site developed for scientists and medical specialists and contains both general and highly technical information. Access is free.
- • Natural History Study: In 2006, the Greenwood Genetic Center in South Carolina, USA began the first ever Natural History Study for Mucolipidosis. ISMRD subsequently partnered with the lead investigator Dr Sara Cathey and the Greenwood Genetic Center to extend the Natural History Study to the other eight diseases that ISMRD supports. Numerous publications resulted from the data gathered. The latest is a paper that has just been released concerning intellectual functioning in Alpha-Mannosidosis. Written by Dr Cathey, the paper discusses the findings of the study of the IQ of 12 patients with Alpha-Mannosidosis and data collected from 31 cases from the literature. Read the paper here.
Patient Support Groups
- • ISMRD is the international support group for Alpha-Mannosidosis
- • ISMRD’s Facebook page; this is our closed group for families only
- • ISMRD’s Public Facebook page for this disorder
- • UK MPS Society is a support group for MPS and related diseases in the United Kingdom
- Other MPS groups around the world will also offer support.