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Fucosidosis is an autosomal recessive lysosomal storage disorder caused by reduced or absent alpha-L-fucosidase enzyme activity. This enzyme is involved in degrading asparagine-linked, fucose-containing complex molecules (oligosaccharides, glycoasparagines) present in cells. Reduced or absent activity of this enzyme results in the abnormal accumulation of these undigested molecules in the tissues and body fluids. Although the disorder is pan ethnic, the majority of reported patients with fucosidosis have been from Italy and the southwestern United States. To date, about 100 cases have been reported worldwide.
Severe and mild subgroups of fucosidosis, designated types I and II, have been described, although recent data suggests individual patients may represent a continuum within a wide spectrum of severity. The more severe type is characterized by infantile onset, rapid psychomotor regression, and severe neurologic deterioration. Additionally, dysostosis multiplex and elevated sweat sodium chloride are frequent findings. Death typically occurs within the first decade of life. Those with the milder phenotype express comparatively mild psychomotor and neurologic regression, radiologic signs of dysostosis multiplex, and skin lesions (angiokeratoma corporis diffusum). Normal sweat salinity, the presence of the skin lesions, and survival into adulthood most readily distinguish milder from more severe phenotypes.
An initial diagnostic workup includes a multienzyme screening assay for several oligosaccharidoses, including fucosidosis, in leukocytes or fibroblasts (OLIWB / Oligosaccharidoses Screen, Leukocytes or OLITC / Oligosaccharidoses Screen, Fibroblasts). If the screening assay is suggestive of fucosidosis, enzyme analysis of alpha-L-fucosidase can confirm the diagnosis.
Enzyme analysis should be pursued in cases with strong clinical suspicion regardless of the screening result. Sequencing of FUCA1 allows for detection of disease-causing mutations in affected patients and identification of familial mutations allows for testing of at-risk family members.
Diagnosis of fucosidosis
Low alpha-fucosidase suggests fucosidosis when accompanied with clinical findings. Some patients exhibit measurable activity minimally below the normal range. These patients are not likely to have fucosidosis.
Low alpha-fucosidase variants in serum have been shown in the absence of fucosidosis. Though this has been associated with ovarian cancer, it is not a consistent finding and makes serum testing for fucosidosis unreliable.
The current laboratory procedure is to be used for disease testing only. Because normal individuals may exhibit rather low levels of alpha-fucosidase activity, carrier status detection by this method is not possible.
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).
> or =0.41 nmol/min/mg protein
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2. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 747-748
3. Thomas GH. Disorders of Glycoprotein Degradation: Alpha-Mannosidosis, Beta-Mannosidosis, Fucosidosis, and Sialidosis. Edited by Valle D, Beaudet AL, Vogelstein B, et al. New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642875. Accessed April 20, 2015.
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