Alpha-mannosidosis
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https://hdl.handle.net/10037/2139Date
2008-07-23Type
Journal articleTidsskriftartikkel
Peer reviewed
Abstract
Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency,
facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in
approximately 1 of 500,000 live births. The children are often born apparently normal, and their
condition worsens progressively. Some children are born with ankle equinus or develop
hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent
infections, especially in the first decade of life), skeletal abnormalities (mild-to-moderate dysostosis
multiplex, scoliosis and deformation of the sternum), hearing impairment (moderate-to-severe
sensorineural hearing loss), gradual impairment of mental functions and speech, and often, periods
of psychosis. Associated motor function disturbances include muscular weakness, joint
abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded
eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight
strabismus is common. The clinical variability is significant, representing a continuum in severity.
The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited
in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on
chromosome 19 (19 p13.2-q12). Diagnosis is made by measuring acid alpha-mannosidase activity in
leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary
secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses
are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic
counseling should be given to explain the nature of the disease and to detect carriers. Antenatal
diagnosis is possible, based on both biochemical and genetic methods. The management should be
pro-active, preventing complications and treating manifestations. Infections must be treated
frequently. Otolaryngological treatment of fluid in the middle ear is often required and use of
hearing aids is invariably required. Early educational intervention for development of social skills is
needed and physiotherapy is important to improve bodily function. Orthopedic surgery may be
necessary. The long-term prognosis is poor. There is an insidiously slow progression of
neuromuscular and skeletal deterioration over several decades, making most patients wheel-chair
dependent. No patients manage to be completely socially independent. Many patients are over 50
years of age.
Publisher
BioMed CentralCitation
Orphanet Journal of Rare Diseases 2008, 3:21Metadata
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