Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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, fewer than 80 patients have been reported in the literature.
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.
A diagnostic workup can include either urine thin-layer chromatography, which may reveal the characteristic banding pattern associated with fucosidosis, or a leukocyte oligosaccharidoses screen (OLIWB / Oligosaccharidoses Screen, Leukocytes), which may demonstrate low alpha-L-fucosidase activity. The fibroblast enzyme assay of alpha-L-fucosidosis can confirm the diagnosis. Enzyme analysis should be pursued in cases with strong clinical suspicion regardless of the urine 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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).
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 =0.41 nmol/min/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Cowan TM, Yu C: Laboratory investigations of inborn errors of metabolism. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 867-868
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. In Scriver's The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Edited by AL Beaudet, B Vogelstein, D Valle, et al. The McGraw-Hill Companies, Inc. Retrieved 4/2014. Available from URL: http://ommbid.mhmedical.com/content.aspx?bookid=474§ionid=45374141
4. Barlow JJ, DiCioccio RA, Dillard PH, et al: Frequency of an allele for low activity of alpha-L-fucosidase in sera: possible increase in epithelial ovarian cancer patients. J Natl Cancer Inst 1981 Nov;67(5):1005-1009