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Genetics Home Reference: your guide to understanding genetic conditions
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Alpha-mannosidosis

Reviewed December 2007

What is alpha-mannosidosis?

Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Signs and symptoms of alpha-mannosidosis include 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.

Signs of alpha-mannosidosis may appear in infancy with rapid progression and severe neurological deterioration. Early-onset alpha-mannosidosis is typically fatal during childhood. In the most severe cases, an affected fetus may die before birth.

Some individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The mildest cases may be detected only through laboratory testing and result in few if any symptoms.

How common is alpha-mannosidosis?

Alpha-mannosidosis is believed to occur in approximately 1 in 500,000 people worldwide.

What genes are related to alpha-mannosidosis?

Mutations in the MAN2B1 gene cause alpha-mannosidosis.

The MAN2B1 gene provides instructions for making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are compartments that digest and recycle materials in the cell. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides containing a sugar molecule called mannose.

Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides accumulate in the lysosomes and cause cells to malfunction and eventually die, resulting in the signs and symptoms of alpha-mannosidosis.

Related Gene(s)

Changes in this gene are associated with alpha-mannosidosis.

  • MAN2B1

How do people inherit alpha-mannosidosis?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of alpha-mannosidosis?

These resources address the diagnosis or management of alpha-mannosidosis and may include treatment providers.

  • Gene Review: Alpha-Mannosidosis (http://www.ncbi.nlm.nih.gov/books/NBK1396/)
  • Genetic Testing Registry: Deficiency of alpha-mannosidase (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0024748)

You might also find information on the diagnosis or management of alpha-mannosidosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/alpha-mannosidosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about alpha-mannosidosis?

You may find the following resources about alpha-mannosidosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for alpha-mannosidosis?

  • alpha-D-mannosidosis
  • alpha-mannosidase B deficiency
  • alpha-mannosidase deficiency
  • Deficiency of alpha-mannosidase
  • lysosomal alpha B mannosidosis
  • lysosomal alpha-D-mannosidase deficiency
  • mannosidosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about alpha-mannosidosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding alpha-mannosidosis?

anxiety ; ataxia ; autosomal ; autosomal recessive ; bone density ; cataract ; cell ; deficiency ; depression ; enzyme ; fetus ; gene ; gums ; hallucinations ; hepatosplenomegaly ; hydrocephalus ; mannose ; molecule ; motor ; neurological ; oligosaccharides ; osteopenia ; progression ; recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Berg T, Riise HM, Hansen GM, Malm D, Tranebjaerg L, Tollersrud OK, Nilssen O. Spectrum of mutations in alpha-mannosidosis. Am J Hum Genet. 1999 Jan;64(1):77-88. (http://www.ncbi.nlm.nih.gov/pubmed/9915946?dopt=Abstract)
  • Gene Review: Alpha-Mannosidosis (http://www.ncbi.nlm.nih.gov/books/NBK1396/)
  • Gotoda Y, Wakamatsu N, Kawai H, Nishida Y, Matsumoto T. Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis. Am J Hum Genet. 1998 Oct;63(4):1015-24. (http://www.ncbi.nlm.nih.gov/pubmed/9758606?dopt=Abstract)
  • Grewal SS, Shapiro EG, Krivit W, Charnas L, Lockman LA, Delaney KA, Davies SM, Wenger DA, Rimell FL, Abel S, Grovas AC, Orchard PJ, Wagner JE, Peters C. Effective treatment of alpha-mannosidosis by allogeneic hematopoietic stem cell transplantation. J Pediatr. 2004 May;144(5):569-73. (http://www.ncbi.nlm.nih.gov/pubmed/15126988?dopt=Abstract)
  • Gutschalk A, Harting I, Cantz M, Springer C, Rohrschneider K, Meinck HM. Adult alpha-mannosidosis: clinical progression in the absence of demyelination. Neurology. 2004 Nov 9;63(9):1744-6. (http://www.ncbi.nlm.nih.gov/pubmed/15534274?dopt=Abstract)
  • Hansen G, Berg T, Riise Stensland HM, Heikinheimo P, Klenow H, Evjen G, Nilssen Ø, Tollersrud OK. Intracellular transport of human lysosomal alpha-mannosidase and alpha-mannosidosis-related mutants. Biochem J. 2004 Jul 15;381(Pt 2):537-46. (http://www.ncbi.nlm.nih.gov/pubmed/15035660?dopt=Abstract)
  • Lyons MJ, Wood T, Espinoza L, Stensland HM, Holden KR. Early onset alpha-mannosidosis with slow progression in three Hispanic males. Dev Med Child Neurol. 2007 Nov;49(11):854-7. Erratum in: Dev Med Child Neurol. 2008 Jan;50(1):32. (http://www.ncbi.nlm.nih.gov/pubmed/17979865?dopt=Abstract)
  • Malm D, Pantel J, Linaker OM. Psychiatric symptoms in alpha-mannosidosis. J Intellect Disabil Res. 2005 Nov;49(Pt 11):865-71. (http://www.ncbi.nlm.nih.gov/pubmed/16207285?dopt=Abstract)
  • OMIM: MANNOSIDOSIS, ALPHA B, LYSOSOMAL (http://omim.org/entry/248500)
  • Pittis MG, Montalvo AL, Heikinheimo P, Sbaragli M, Balducci C, Persichetti E, Van Maldergem L, Filocamo M, Bembi B, Beccari T. Funtional characterization of four novel MAN2B1 mutations causing juvenile onset alpha-mannosidosis. Clin Chim Acta. 2007 Jan;375(1-2):136-9. Epub 2006 Jul 6. (http://www.ncbi.nlm.nih.gov/pubmed/16919251?dopt=Abstract)
  • Sbaragli M, Bibi L, Pittis MG, Balducci C, Heikinheimo P, Ricci R, Antuzzi D, Parini R, Spaccini L, Bembi B, Beccari T. Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis. Hum Mutat. 2005 Mar;25(3):320. (http://www.ncbi.nlm.nih.gov/pubmed/15712269?dopt=Abstract)
  • Sun H, Wolfe JH. Recent progress in lysosomal alpha-mannosidase and its deficiency. Exp Mol Med. 2001 Mar 31;33(1):1-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11322479?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2007
Published: April 17, 2014