|Values are valid only on day of printing.|
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 with onset in early infancy, skeletal abnormalities (dysostosis multiplex), and severe central nervous system involvement. Although treatment is mostly supportive and aimed at preventing complications, hematopoietic stem cell transplant has been reported to be a feasible therapeutic option. 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.
Diagnosis of alpha-mannosidosis
Values <0.54 nmol/min/mg protein are consistent with a diagnosis of alpha-mannosidosis.
This test cannot be used to establish carrier status for alpha-mannosidosis.
> or =0.54 nmol/min/mg protein
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Bone Marrow Transplant 2012 Mar;47(3):352-359. DOI: 10.1038/bmt.2011.99