Fucosidosis is a rare

lysosomal storage disorder Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

in which the FUCA1 gene experiences mutations that severely reduce or stop the activity of the

alpha-L-fucosidase In enzymology, an alpha-L-fucosidase () is an enzyme that catalyzes the chemical reaction :an alpha-L-fucoside + H2O \rightleftharpoons L-fucose + an alcohol Thus, the two substrates of this enzyme are alpha-L-fucoside and H2O, whereas its ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

.Genetics Home Reference
/ref> The result is a buildup of complex sugars in parts of the body, which leads to death. Fucosidosis is one of nine identified

glycoprotein storage diseases Glycoproteinosis are lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function. The term is sometimes reserved for conditions involving degradation of glycoproteins. Types * (E77.0) Defects in post-translatio ...

. The gene encoding the alpha-fucosidase, FUCA 1, was found to be located to the short arm of chromosome 1p36 - p34,The Medical Biochemistry Page
/ref> by Carrit and co-workers, in 1982.

Cause

Fucosidosis is an autosomal recessive disorder that affects many areas of the body. Mutations in the FUCA1 gene causes fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. The enzyme plays a role in the breakdown of complex sugars in the body. The disorder is characterized by lysosomal accumulation of a variety of glycoproteins, glycolipids, and oligosaccharides that contain

fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...

moieties. The deficiency of the enzyme

, which is used to metabolize complex compounds in the body (fucose-containing

glycolipids Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the conne ...

and fucose-containing

glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

). With the lack of this enzyme activity, the result is incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds accumulate in various parts of the body and begin to cause malfunction in cells, and can eventually cause cell death. Brain cells are especially sensitive to this buildup. Other results are progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease, and coarsening of facial features.Webmd Children's Health
/ref> Fucosidosis is the consequence of faulty degradation of both

sphingolipids Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because ...

and

polysaccharides Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...

. Major accumulation of the H-antigen (a member of the ABO blood group antigens), a glycolipid, is seen primarily in the liver of fucosidosis patients.

Diagnosis

Diagnosis: A special urine test is available to check for any partially broken-down-sugars. If they are present, a skin or blood sample will be taken to test for below-normal amounts of alpha-fucosidase. - Fucosidosis is an autosomal recessive disorder, which means that both parents have to have the mutation and pass it on to the child. When both parents have the mutation, there is a 25% chance of each child having fucosidosis.

Type 1

Type 1 usually begins somewhere in the first three to 18 months of age and in considered the most severe of the three types.about.com
/ref> Symptoms include: * Coarse facial features * Enlarged liver, spleen, and/or heart * Intellectual disability * Seizures * Abnormal bone formation of many bones * Progressive deterioration of brain and spinal cord * Increased or decreased perspiration Patients have no vascular lesions, but have rapid psychomotor regression, severe and rapidly progressing neurologic signs, elevated sodium and chloride excretion in the sweat, and fatal outcome before the sixth year.

Type 2

Type 2 appears when a child is around 18 months of age and in considered milder than Type 1 but still severe. Symptoms include: * Symptoms similar to Type 1 but milder and progress more slowly.

Type 3

Type 3 appears around 1–2 years of age and is considered mild.

Treatment

Treatment: There is no treatment or way to reverse the disease. Treatment will focus on the symptoms an individual has, such as seizure medication. * It is possible that if an individual receives a bone marrow transplant, they could receive healthy bone marrow cells which would produce normal amounts of fucosidase. But there not is enough research to prove this is an effective treatment.

History

Fucosidosis is an extremely rare disorder first described in 1962 in two Italian siblings who showed progressive intellectual disability and neurological deterioration. The disease itself is extremely rare (less than 100 documented cases) only affecting 1:2,000,000, with most cases being occurring in Italy, Cuba, and the southwest U.S. The disease has three different types. Type 1 and 2 are considered severe, and Type 3 being a mild disease. Symptoms are highly variable with mild cases being able to live to within the third or fourth decade. Type 1 and 2 are both linked with mental retardation. Severe cases can develop life-threatening complications early in childhood. Because the major accumulating glycoconjugate in fucosidosis patients is the blood group H-antigen, it is intriguing to speculate, but the evidence is not clear at this time, that blood type may affect the course of the disease.

Other forms

Canine fucosidosis is found in the

English Springer Spaniel The English Springer is a breed of gun dog in the Spaniel group traditionally used for flushing and retrieving game. It is an affectionate, excitable breed with a typical lifespan of twelve to fourteen years. They are very similar to the Wels ...

. Typically affecting dogs between 18 months and four years, symptoms include: * Loss of learned behavior * Change in temperament * Blindness * Loss of balance * Deafness * Weight loss * From the onset, disease progress is quick and fatal. Just like the human version, canine fucosidosis is a recessive disorder and two copies of the gene must be present, one from each parent, in order to show symptoms of the disease.

References

External links

* http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1095/viewAbstract - Rare diseases.org {{Glycoproteinoses Rare diseases Autosomal recessive disorders Glycoprotein metabolism disorders Skin conditions resulting from errors in metabolism