What is Fucosidosis?
Fucosidosis is one of nine identified Glycoprotein Storage Diseases. These inherited diseases are part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many different oligosaccharides (long sugar chains). These sugar chains are continuously made and broken down in our bodies, and this process is necessary for appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the sugar chains.
When an enzyme is not working, it leads to the build up of the sugar chains in the lysosome. In Fucosidosis, the specific enzyme that is absent is called alpha- fucosidase. The build up of oligosaccharide sugars that is caused, is gradual and interferes with the correct function of the cell. This build up is gradual and eventually leads to the clinical features of Fucosidosis. Features may progress in severity over time.
In Fucosidosis, the specific enzyme that is absent is called alpha-fucosidase.
There are two different types of Fucosidosis. They are characterized by the age of onset and type of physical and mental manifestations. Type I usually presents in the first 3–18 months of life with features typical of lysosomal storage diseases including coarsening of facial features, organomegaly (large liver, spleen and/or heart), and dysostosis multiplex (abnormal bone formation that is found in multiple bones of the body) seen on x-ray. Cherry red spots may be present on ophthalmology evaluation. Cherry red spots are spots on the retina that have storage of sugar chains, causing the remainder of the healthy retina to look brighter. Mental retardation and seizures are also present. Additionally, sweat chloride may be elevated.
Type II Fucosidosis presents between 12 and 24 months of life. Individuals usually have mild coarsening of facial features, dysostosis multiplex, mental retardation and organomegaly. In addition, angiokeratomas (superficial blood vessel dilation over which wartlike growths occur) may be present. Another feature of type II Fucosidosis is the presence of twisted blood vessels within the membrane covering of the eyeball and inner eyelid.
Fucosidosis is not contagious and cannot be “caught.” It is a genetic condition, which means that it is caused by a change in the instructions that direct the way our bodies grow and develop. These instructions are called genes. People have two copies of all their genes, including the gene for Fucosidosis (alpha- fucosidase). One copy is inherited from the mother in the egg, and one from the father in the sperm.
Only when there is a change in the gene code is there a possibility that the disease will occur. For a person to have Fucosidosis, they must inherit changes in both of their alpha-fucosidase genes resulting in instructions that do not function properly. This is known as autosomal recessive inheritance.
For a couple to have a child with Fucosidosis, both parents must have at least one changed copy of the alpha-fucosidase gene which they both pass on to their child. Parents do not have control over which genes they pass on to their children.
If a person has one changed copy of the alpha-fucosidase gene and one normal copy of the alpha-fucosidase gene they are said to be a “carrier” of the condition and will not show any symptoms of Fucosidosis. If two parents are both carriers, they have a 1 in 4 (25%) chance of having a child with Fucosidosis in each pregnancy.
Testing for Glycoprotein storage diseases is typically performed in conjunction with a genetics evaluation. A genetics team takes into account the medical history and clinical features of a patient to determine what type of genetic testing is appropriate. For the diagnosis of an Glycoprotein storage disease, a urine test should show increased oligosaccharides. To determine if the patient has Fucosidosis, the urine test should be followed by a blood test or skin biopsy. The blood or skin sample should show decreased amounts of the enzyme alpha- fucosidase.
For families who have had a child diagnosed with Fucosidosis, prenatal diagnosis is available in future pregnancies by looking at alpha-fucosidase activity through Chorionic Villus Sampling (CVS) or amniocentesis. Prenatal diagnosis by detection of alpha-fucosidase gene changes is also available for families in which the responsible gene changes have been identified.