Diagnosis of alpha-mannosidosis
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Diagnostic testing. Not recommended for carrier detection.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Alpha-mannosidosis is an autosomal recessive lysosomal storage disorder caused by reduced or absent acid alpha-mannosidase enzyme activity. This enzyme is involved in glycoprotein catabolism, with absent or reduced activity resulting in the accumulation of undigested mannose-containing complex oligosaccharides in the lysosomes, disrupting the normal functioning of cells.
Clinical features and severity of symptoms are widely variable within alpha-mannosidosis, but in general, the disorder is characterized by skeletal abnormalities, immune deficiency, hearing impairment, and mental retardation. Three clinical subtypes of the disorder have been described and they vary with respect to age of onset and clinical presentation. Type 1 is generally classified by a mild presentation and slow progression with onset after 10 years of age and absence of skeletal abnormalities. Type 2 is generally a more moderate form with slow progression and onset prior to 10 years of age with skeletal abnormalities and myopathy. Type 3 is the most severe form and usually presents with prenatal loss or severe central nervous system involvement leading to an early death. The incidence of alpha-mannosidosis is estimated at 1 in 500,000 live births.
A diagnostic work up for alpha-mannosidosis may demonstrate slight elevations of oligosaccharides in urine (OLIGO / Oligosaccharide Screen, Urine). Reduced or absent enzyme activity of acid alpha-mannosidase in leukocytes can confirm a diagnosis. Sequencing of the MAN2B1 gene allows for detection of disease-causing mutations in affected patients and identification of familial mutations allows for testing of at-risk family members.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =0.53 nmol/min/mg protein
This enzyme is deficient in alpha-mannosidosis.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test cannot be used to establish carrier status for alpha-mannosidosis.
Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Malm D, Nilssen O: Alpha-mannosidosis. Orphanet J Rare Dis 2008 Jul 23;3:21
2. Thomas GH: Disorders of glycoprotein degradation: In The Metabolic and Molecular Basis of Inherited Disease. Vol 3. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 3507-3533