Fucosidosis is an extremely rare lysosomal storage disease, characterrised by a deficiency of the enzyme alpha-L-fucosidase. Fucosidosis is inherited as an autosomal recessive genetic trait. Fucosidosis types 1 and 2 may occur in the same family. The gene has been localised at 1p36- p34 (locus FUCA 1), but there is also a pseudogene on chromosome 2, and the FUCA 2 gene, localised on chromosome 6, regulating the activity of alpha-L-fucosidase in fibroblasts. Over 20 mutations have been identified so far.
Low levels of the alpha-L-fucosidase enzyme lead to the abnormal accumulation of certain fucose-containing complex compounds (i.e., glycosphingolipids, glycolipids, and glycoproteins) in many tissues of the body. There are two relevant types of fucosidosis, determined mainly by the time of onset and severity of clinical symptoms. Some scientists theorise there are three types, with the age of onset and the disease severity being the determining factors.
The symptoms of fucosidosis type 1, the most severe form of the disease, may become apparent between 3 and 18 months of age. Symptoms may include progressive deterioration of the central nervous system, mental retardation, loss of previously acquired intellectual skills, seizures and growth retardation leading to short stature. Other abnormalities become apparent over time including multiple deformities of the bones (dysostosis multiplex), ovoid breaking vertebrae with kyphoscoliosis, coarse facial features (Hurler-like appearance), cardiomegaly and hepatosplenomegaly. Additional symptoms may include malfunction of the gallbladder, salivary and sweat glands that produce sweat with high NaCl content. Death usually occurs during the first decade of life.
In fucosidosis type 2, deterioration of the central nervous system becomes apparent after the first years of life; symptoms may be similar but milder and progress more slowly than in type 1, and sweat salinity is normal. Dystonia, progressive deafness and tortuous conjunct-tival vessels are present. The most noticeable feature distinguishing fucosidosis type 1 from type 2 is the appearance of angiokeratomas on the skin around 10 years of age in those individuals with type-2 disease.