About fucosidase deficiency

What is fucosidase deficiency?

Fucosidosis is a rare genetic disorder characterized by deficiency of the enzyme alpha-L-fucosidase, which is required to break down (metabolize) certain complex compounds (e.g., fucose-containing glycolipids or fucose-containing glycoproteins). Fucose is a type of the sugar required by the body to perform certain functions (essential sugar). The inability to breakdown fucose-containing compounds results in their accumulation in various tissues in the body. Fucosidosis results in progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease and coarsening of facial features. 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.

The disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain fats and carbohydrates. Low levels or inactivity of the alpha-L-fucosidase enzyme leads to the abnormal accumulation of fucose-containing compounds in the tissues of individuals with fucosidosis.

What are the symptoms for fucosidase deficiency?

Weak reflex symptom was found in the fucosidase deficiency condition

The symptoms of fucosidosis vary greatly even among individuals within the same family. Fucosidosis can be rapidly progressive causing severe, life-threatening complications in children or develop during adolescence and progress more slowly eventually causing serious complications in adulthood. In the past, fucosidosis was sometimes separated in type I and type II. However, researchers now believe that fucosidosis represents a disease spectrum with a wide variety of expression. Cases labeled fucosidosis type I (early onset, rapid progression) represent the severe end of the spectrum and those labeled fucosidosis type II represent the mild end.

Infants with severe forms of fucosidosis may not exhibit any symptoms until 6 months to one year of life. Initial symptoms may be associated with mental and motor deterioration such as delayed acquisition of skills required to coordinate mental and muscular activities (psychomotor retardation). Physicals findings may also develop including coarse facial features, thickened lips and tongue, multiple deformities of the bone (mild dysostosis multiplex), loss of muscle tone (hypotonia) resulting in “floppiness” and growth retardation. Progressive neurological deterioration may result in a variety of symptoms including intellectual disability, various movement disorders and/or uncontrolled rigid extensions and rotations of the arms, legs, fingers, and toes (decerebrate rigidity). Severe fucosidosis often progresses to cause life-threatening neurodegenerative complications and/or severe, progressive loss of weight and muscle mass (cachexia), usually within the first few years of life.

Less common findings associated with severe forms of fucosidosis include abnormally enlarged internal organs (visceromegaly), such as the liver and spleen (hepatosplenomegaly) or heart (cardiomegaly), Seizures, hearing loss, abnormal curvature of the spine (kyphoscoliosis), and repeated respiratory infections. Some affeced individuals may sweat excessively and their sweat may contain abnormally high levels of salt.

In some less severe cases, the symptoms associated progressive deterioration of the central nervous system may not become obvious until the age of 18 months to three years. The symptoms of less severe forms of fucosidosis are similar to the more severe forms, but tend to be milder with slower progression. Affected individuals may develop wart-like growths (angiokeratomas) on the skin around the age of two years. These lesions occur mainly on the abdomen, buttocks, thighs, and/or external genitalia. Some individuals may experience fixation of certain joints in a permanently flexed position (contractures), involuntary muscle spasms (spasticity) that result in slow, stiff movements of the legs and inadequate ability to sweat (anhidrosis). Individuals with less severe forms of fucosidosis may live well into their second, third or fourth decades before the disorder progresses to cause life-threatening complications.

What are the causes for fucosidase deficiency?

Fucosidosis is caused by disruptions or changes (mutations) of the alpha-L-fucosidase (FUCA1) gene resulting in deficiency of the alpha-L-fucosidase enzyme. The symptoms of fucosidosis occur as a result of excessive accumulation of fucose-containing compounds (e.g., certain glycosphingolipids or certain glycoproteins) in the body due to abnormally low levels of this enzyme. Researchers do not know why the symptoms and severity vary so greatly in individuals with fucosidosis. Some researchers believe that mutation of the FUCA1 gene in combination with certain genetic and environmental factors all play a role in the severity of the disease in individuals. More research is necessary to determine what these factors may be.

Individuals with fucosidosis also have a pseudogene- a gene that can no longer creates proteins or is no longer expressed in the body. The pseudogene associated with fucosidosis is called FUCA1P.

Fucosidosis is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

What are the treatments for fucosidase deficiency?


The treatment of fucosidosis is directed toward the specific symptoms that are apparent in each individual. For example, antibiotic therapy may be administered to treat recurrent respiratory infections or fluid replacement may be considered to counter the effects of dehydration that may occur due to excessive sweating. A team approach for individuals with fucosidosis may be necessary and may include special social support and other medical services. Genetic counseling is recommended for affected individuals and their families.

What are the risk factors for fucosidase deficiency?

Fucosidosis/fucosidase deficiency is brought about by transformations in genes known as FUCA1, which gives directions to the development of a protein called alpha-L-fucosidase.

  • Alpha-L-fucosidase for the most part, works in a cell's lysosomes and is liable for the breakdown and reusing of explicit complex sugars connected to protein and fat particles.
  • The genes which came hereditary in FUCA1 quality impede the capacity of alpha-L-fucosidase to carry out its role accurately, prompting an amassing of complicated sugar particles in cells that ultimately make cells break down.
  • This hereditary condition is acquired in the pattern of autosomal recessiveness, and that implies that an impacted youngster has gotten one flawed duplicate of the FUCA1 quality from every one of their folks.
  • Fucosidosis is brought about by disturbances or changes (transformations) of the alpha-L-fucosidase (FUCA1) quality bringing about a lack of the alpha-L-fucosidase protein.
  • The side effects of fucosidosis happen because of over-the-top amassing of fucose-containing compounds (e.g., certain glycosphingolipids or certain glycoproteins) in the body because of strangely low levels of this protein.
  • Analysts don't have even the slightest idea why the side effects and seriousness shift so extraordinarily in people with fucosidosis.
  • A few specialists accept that transformation of the FUCA1 quality in blend with specific hereditary and ecological factors all assume a part in the seriousness of the sickness in people.
  • More examination is important to figure out what these elements might be.

Sugar buildup in different body organs,Delayed motor skills,Weak reflex,Rapidly progressive illness
Intellectual disability,Slow growth of body and brain,Abnormal skeletal development,Recurrent respiratory infections

Is there a cure/medications for fucosidase deficiency?

Fucosidosis deficiency is a genetic disorder that has a deficiency of the alpha-L-fucosidase enzyme. This enzyme helps to metabolize a few complex compounds such as fucose-containing glycoproteins or fucose-containing glycolipids. The glucose (sugar) buildup affects various body organs including the brain and nervous system. Moreover, it may also reflect symptoms like intellectual disability, abnormal skeletal development, clusters of small, dark red spots on the skin, etc. Unfortunately, there are no approved treatments or therapy that can reverse the effects of fucosidosis deficiency.

Video related to fucosidase deficiency