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 available 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 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.
An initial diagnostic workup includes a multienzyme screening assay for several oligosaccharidoses, including mannosidosis in leukocytes or fibroblasts (OLIWB / Oligosaccharidoses Screen, Leukocytes or OLITC / Oligosaccharidoses Screen, Fibroblasts). If the screening assay is suggestive of alpha-mannosidosis, enzyme analysis of acid alpha-mannosidase can confirm the diagnosis.
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 =0.54 nmol/min/mg protein
Values <0.54 nmol/min/mg protein are consistent with a diagnosis of 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.
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, D Valle, et al. New York, McGraw-Hill Book Company, 2001 pp 3507-3533