What Is Fucosidosis?
Fucosidosis, also known as an alpha-L-fucosidase deficiency, is a rare condition occurring due to a deficiency of the enzyme alpha-L fucosidase. This enzyme is crucial for the metabolism of certain complex compounds (fucose-containing compounds). The condition is characterized by an inability to break down or metabolize fucose-containing compounds. Fucosidosis belongs to a group of disorders called lysosomal storage disease. Cells include membrane-bound particles called lysosomes that serve as the cell's central digestive units. Nutrients such as specific fat and carbohydrates are broken down or digested by enzymes within lysosomes. The tissues of fucosidosis patients abnormally accumulate fucose-containing substances due to low or inactive levels of the alpha-L-fucosidase enzyme. Fucosidosis affects several parts of the body, specifically the brain. Fucosidosis causes skeletal disorders, coarse facial features, developmental delay, stunted growth, abnormal skin, and progressive neurological degeneration. The intellectual incapacity of those who are affected worsens with age, and many go on to develop dementia (a cluster of disorders affecting memory and thinking capacity).
What Are the Types of Fucosidosis?
According to symptoms and age of beginning, researchers identified two forms of fucosidosis; however, the latest theories suggest that the two categories are one condition with a wide range of signs and symptoms. The two types are:
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Fucosidosis Type 1: It is a severe and infantile form of the condition. This type usually manifests between three to 18 months after birth.
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Fucosidosis Type 2: It is the milder form of the condition with delayed manifestation. The symptoms start showing after 18 months of age.
Who Is Affected by Fucosidosis?
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Fucosidosis is an extremely rare disorder, and approximately only 100 cases have been reported globally.
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Fucosidosis is prevalent in the southern parts of Italy, Cuba, and southwestern parts of the United States of America.
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The condition does not show gender bias, affecting men and women equally.
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According to one estimate, the incidence rates are less than 1 per 200,000 births. However, researchers believe that the condition is heavily underdiagnosed; therefore, the exact incidence rate of fucosidosis is uncertain.
Is Fucosidosis an Inherited Condition?
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Yes, fucosidosis is an inherited disorder which means the condition is genetically passed down from parents to their children.
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Fucosidosis is inherited in an autosomal recessive pattern, which means the condition develops when both parents carry a copy of the defective gene. However, the parents may not show any signs and symptoms of the disease because they are only carriers.
What Causes Fucosidosis?
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Fucosidosis is a genetic disorder due to changes or mutations in the FUCA1 gene (alpha-L-fucosidase gene).
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The FUCA1 gene is responsible for providing information for the production of the alpha-L-fucosidase enzyme.
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Alpha-L-fucosidase activity is significantly decreased or completely lost due to FUCA1 gene mutations. The breakdown of glycolipids and glycoproteins is incomplete when there is insufficient enzyme activity. These partially metabolized substances eventually collect in several body tissues and cells, leading to cell dysfunction.
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Some researchers believe that the FUCA1 gene mutation and other genetic and environmental factors contribute to the severity of the disease in individuals. However, more research is required to identify these risk factors.
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Pseudogenes, genes that can no longer make proteins or are no longer expressed in the body, are also present in people with fucosidosis. The pseudogene present in the case of fucosidosis is known as FUCA1P.
What Are the Symptoms of Fucosidosis?
Even among members of the same family, there are significant differences in the symptoms of fucosidosis. Fucosidosis can progress rapidly and cause serious, life-threatening consequences in children. However, during adolescence, the condition progresses at a slower rate and subsequently causes severe complications in adulthood.
The symptoms of fucosidosis are:
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Infants with fucosidosis may not start showing symptoms for six to 12 months after birth.
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Mental degradation.
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Motor skill deterioration.
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Psychomotor retardation (delayed learning of the abilities needed to combine physical and mental activity).
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The coarseness of the facial features.
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Thick lips and tongue.
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Multiple bone deformities.
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Hypotonia (loss of muscle tone).
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Retarded growth.
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Intellectual disability due to progressive neurological degradation.
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Movement disorders.
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Weight loss.
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Cachexia (loss of muscle mass).
Less common symptoms of fucosidosis include:
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Enlargement of organs.
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Seizures (sudden electrical disturbance of the brain).
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Loss of hearing.
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Kyphoscoliosis (abnormal spine curvature).
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Recurrent respiratory infections.
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Excessive sweating with unusually high levels of salt in the sweat.
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Symptoms of less severe fucosidosis are comparable to those of more severe forms; they typically start milder and proceed more slowly.
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Wart-like skin growths.
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Muscle spasms that are involuntary.
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Some people could have specific joints fixed in a permanently flexed state.
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Less severe forms of fucosidosis can cause people to survive long into their second, third, or fourth decades before the condition worsens and poses a threat to their lives.
How Is Fucosidosis Diagnosed?
The diagnosis of fucosidosis is confirmed when:
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Clinical Examination: Infants with skeletal deformities during the first year of life that are accompanied by neurological deterioration and intellectual incapacity may be suspected of having fucosidosis. A thorough clinical examination, a complete patient history, and several specialized tests could be used to confirm the diagnosis.
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Electron Microscopic Examination: When tissue samples from the skin, liver, spleen, heart, lung, kidney, sweat glands, and other cells are examined under an electron microscope, atypical "cavities" (vacuoles) within these cells may be seen. These vacuoles may be transparent or contain thin, disc-like structures or granules that resemble sand.
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Imaging Tests: Modern imaging methods, such as computer-assisted tomography (CT scan) and magnetic resonance imaging (MRI), can confirm the degeneration of the brain's white matter.
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Urine Examination: To check for any partially metabolized sugars, a specific urine test is available. Increased quantities of specific fucose-containing complex compounds in the urine may be found through laboratory examination of urine samples. If present, a skin or blood sample will be obtained to check for less than average levels of alpha-fucosidase.
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Enzyme Assays: Enzyme assays on cultured fibroblasts and leukocytes can detect diminished alpha-L-fucosidase activity.
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Chorionic Villus Sampling: Through the use of specific tests such as chorionic villus sampling, fucosidosis can be successfully identified prenatally. During chorionic villus sampling, tissue samples of the fetus are taken, and white blood cells and cultured tissue cells are subjected to enzyme tests.
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Amniocentesis: This test also determines the presence of fucosidosis before birth. An amniocentesis is a procedure where a sample of the fluid that surrounds the growing baby is taken and examined.
How Is Fucosidosis Treated?
The treatment of fucosidosis is done in the following ways:
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The disorder cannot be reversed or treated. The main focus of the treatment is on alleviating the patient's symptoms.
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Recurrent respiratory infections may be treated with antibiotic medication, and fluid replacement therapy may be recommended to prevent dehydration due to excessive sweating.
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Antiseizure drugs may be given to patients who present with symptoms of seizures.
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It is advised that affected individuals and their families seek genetic counseling.
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Some fucosidosis patients have been treated with bone marrow transplantation. However, research is going on to determine this treatment method's efficiency and long-term safety.
Conclusion:
Fucosidosis is an uncommon genetic disorder with a limited number of cases reported to date. The condition belongs to a group of disorders known as lysosomal storage diseases. Fucosidosis is characterized by the reduced amount or diminished activities of the enzyme alpha-L-fucosidase. Depending upon the severity of the symptoms and time of onset, the condition is categorized into two types. The treatment and prognosis of fucosidosis also depend upon the symptoms' severity and the onset time. In severe cases, symptoms frequently start in early childhood, and affected people normally live into their late childhood years. In milder cases, symptoms appear at one to two years old, and affected people typically live into their mid-adult years.
