Fucosidosis: Description, Causes and Risk Factors:
Fucosidosis is an enzyme de?ciency disorder which results in defective fucosidase activity, the accumulation of lipids (fucose-rich oligosaccharides, sphingolipids and glycopeptides chains) and the absence of glycosaminoglycans (GAGs). This accumulation is responsible for many problems.
Fucosidosis is a rare condition; approximately 100 cases have been reported worldwide. This condition appears to be most prevalent in Italy, Cuba, and the southwestern United States.
There are two different types of fucosidosis, Type I and Type II, characterized by the age of onset and by the types of physical and mental manifestations of the disorder.
Type I typically appears in the first three to 18 months of life. Symptoms include coarsening of facial features, a large liver, spleen and/or heart, and abnormal bone deformities. Cherry red spots may be present on the surface of the eye. Mental retardation and seizures are also present. 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 II patients have angiokeratoma, milder psychomotor retardation and neurologic signs, longer survival, and normal salinity in the sweat. The disease often appears between 12 and 24 months of life. Affected children usually have mild coarsening of facial features, abnormal bone deformities, mental retardation, and an enlarged liver, spleen and/or heart. Twisted blood vessels within the membrane covering of the eye and inner eyelid are characteristic features of Type II fucosidosis.
Mutations in the FUCA1 gene cause fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. This enzyme plays a role in the breakdown of complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) and fats (glycolipids). Alpha-L-fucosidase is responsible for cutting (cleaving) off a sugar molecule called fucose toward the end of the breakdown process.
FUCA1 gene mutations severely reduce or eliminate the activity of the alpha-L-fucosidase enzyme. A lack of enzyme activity results in an incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds gradually accumulate within various cells and tissues throughout the body and cause cells to malfunction. Brain cells are particularly sensitive to the buildup of glycolipids and glycoproteins, which can result in cell death. Loss of brain cells is thought to cause the neurological symptoms of fucosidosis. Accumulation of glycolipids and glycoproteins also occurs in other organs such as the liver, spleen, skin, heart, pancreas, and kidneys, contributing to the additional symptoms of fucosidosis.
The symptoms and severity of fucosidosis are highly variable and the disorder represents a disease spectrum in which individuals with mild cases have been known to live into the third or fourth decades. Individuals with severe cases of fucosidosis can develop life-threatening complications early in childhood.
Frequent coughs, colds and throat infections are commonproblems for those suffering from fucosidosis. The tonsilsand adenoids often become enlarged and can partly blockthe airway. For this reason they may be removed.
Babies with fucosidosis may be larger than average atbirth and may grow faster than normal during the ?rst fewyears of life. As they get older, however individuals withfucosidosis will be restricted
in their growth.
Unlike other storage disorders, the facial appearanceof children with fucosidosis can be normal. In others,however their heads may be large and longer than normalfrom front to back. They may also have a protrudingforehead. The nose may be broad with a ?attened bridge.The skull tends to be short and the ears are often largeand low set. Hair may be coarse.
Individuals with fucosidosis may also suffer from neurologicaldeterioration, Psychomotor Retardation being the mostsigni?cant consequence. This is a general reduction in thespeed of thought and difficulty or slowness in movementand speech. The accumulation of Oligosaccharides in thebrain is primarily responsible for the learning difficultiesseen in affected children and adolescents.
In most individuals with fucosidosis the liver andspleen become enlarged by storage of Oligosaccharides(hepatosplenomegaly
). The enlarged organs do notusually cause problems, but they can interfere witheating and breathing.
Diagnosis of fucosidosis is suspected based on the child's physical appearance and symptoms, a special urine test will check for partially-broken-down sugars (oligosaccharides). If they are present, a blood sample or skin sample (biopsy) will be taken. In fucosidosis the blood or skin will have below-normal amounts of alpha-fucosidase in it.
There is as yet no way to stop or reverse fucosidosis, so treatment focuses on the symptoms an individual has, such as medications for seizure control.
It is possible that if an individual with fucosidosis received a bone marrow transplant (BMT), he or she would receive healthy bone marrow cells which would produce normal amounts of alpha-fucosidase. However, only a few individuals with fucosidosis have experimentally received BMT, and not enough information is available to know if it is an effective treatment for fucosidosis.
Enzyme Replacement Therapy (ERT) is based on the principle that the recombinant form of the enzyme that is missing or malfunctioning in individuals with an MPS or Related Disease is given via repeated intravenous infusion in order to reduce the symptoms and clinical manifestations associated with the disease.
Although there is reason to hope that Enzyme Replacement Therapy will help some of the physical problems, the blood-brain barrier may prevent Enzyme Replacement Therapy from directly helping the brain. However ERT for Fucosidosis may be a possibility in the future.
There is a great deal of research being carried out that may lead to possible treatments. Gene therapy (which involves replacing the faulty gene with a copy of a normal gene) may be a realistic possibility in years to come.
NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.