This article includes discussion of fucosidosis, alpha-L-fucosidase deficiency, fucosidase deficiency, and mucolipidosis F. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Fucosidosis is an autosomal recessive disorder resulting from a deficiency of alpha-L-fucosidase, encoded by the FUCA1 gene. Data suggest that individual patients may actually represent a continuum within a wide spectrum of severity. The more severely affected patients have, within the first year of life, the onset of psychomotor retardation, coarse facies, growth retardation, and dysostosis multiplex. The milder phenotypes develop angiokeratoma and have longer survival. The enzyme defect results in the accumulation and excretion of a variety of glycoproteins, glycolipids, and oligosaccharides containing fucoside moieties. Diagnosis can be suspected by the detection of excess oligosaccharides in urine, but must be confirmed by the presence of low alpha-L-fucosidase activity in peripheral white blood cells. MRI and MR spectroscopy are of substantial diagnostic value. Pallidal lesions resembling the eye-of-the-tiger sign suggest brain iron accumulation.
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• Fucosidosis presents as a continuous clinical spectrum of the combination of neurologic deficit and skeletal abnormalities.
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• It is caused by a deficiency of alpha-L-fucosidase, encoded by the FUCA1 gene.
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• Typical MRI features combine bilateral globi pallidi hyperintensity on T1-weighted images that are hypointense on T2-weighted images with diffuse hypomyelination.
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• Proton MR spectroscopy shows specific diagnostic abnormalities in patients with fucosidosis.
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• Early hematopoietic stem cell transplantation should be considered in patients with the less aggressive form of fucosidosis.
Historical note and terminology
Fucosidosis is a progressive mental retardation syndrome involving lysosomal storage that was first described by Durand in 1966 (08; 09) and involves both fuco-oligosaccharide and fuco-glycosphingolipid storage (06). One of the original names for the second patient to be described (27) was "mucolipidosis F," because the phenotype was reminiscent of patients with mucopolysaccharide storage diseases. Other forms of fucosidosis show angiokeratomas reminiscent of Fabry disease (47; 15) without substantial skeletal abnormalities. Unfortunately, numerous phenotypes are unrelated to genotype and the resulting level of residual enzyme activity. The FUCA1 gene, together with a pseudogene, FUCA1P, has been cloned, and numerous mutations have been shown to cause fucosidosis (12; 49; 48; 37; 38; 35; 40).