Introduction

Fucosidosis is a rare inherited disorder that affects the storage of a particular enzyme called alpha-L-fucosidase, which is needed to break down certain sugars attached to proteins in the body, and help keep cells functioning efficiently by processing and recycling these molecules.¹ This condition can be classified as a lysosomal storage disorder, which is characterised by the build-up of toxic compounds in the body due to the enzyme deficiencies. Lysosomes are membrane-bound compartments that store enzymes responsible for breaking down sugars, a process essential for normal mental and physical development of a person.¹ Each enzyme in a lysosome has a specific function when it comes to breaking down sugar chains. When an enzyme is mutated (i.e. faulty), it causes sugar to build up in the lysosome.

Fucosidosis is an autosomal recessive disorder, a genetic condition that occurs when a person inherits two copies of a faulty gene, one from each parent. If a person only has one defective gene and the other is normal, they are considered a carrier (i.e. they have one faulty gene and do not usually show symptoms of the condition). This defect, or mutation, occurs in the FUCA1 gene (full name: alpha-L-fucosidase 1), resulting in the absence of the alpha-L-fucosidase enzyme in lysosomes.²

The risk for two carrier parents to pass the faulty gene and have an affected child is 25% with each pregnancy, and the chance of having a carrier child is 50% with each pregnancy.³ There is a 25% chance that the child will receive normal genes from both parents.

The risk of developing fucosidosis is equal for males and females.³

Without the essential alpha-L-fucosidase enzyme, sugar-containing materials build up in various organs and bring about the symptoms commonly associated with this disease.³

Fucosidosis is believed to have an estimated frequency of less than 200,000 live births.²

The sugar needed by the body to perform certain functions, and associated with fucosidosis when it accumulates in excess, is called fucose.³ When enzymes cannot break down fucose-containing compounds, it results in their accumulation in the body.

Fucosidosis causes brain dysfunction, abnormalities in the skin, stunting of growth, and muscle-related issues. Despite being a genetic disorder that is passed down in families, the symptoms of fucosidosis can vary greatly between family members.³

Diagnosing fucosidosis is not always easy; the preferred method, genetic testing, is limited in certain parts of the world, such as developing countries.² Although genetic testing is the ideal method of diagnosing inherited diseases like fucosidosis, a combination of observing clinical features and symptoms in the patient along with recognising key patterns in MRI findings can help physicians reach a diagnosis.²

Sub-classification of fucosidosis

Fucosidosis is sub-classified into two major types: type one (I) and type two (II).²

Type I is the more severe form of the condition, known to begin around 6 months of age and lead to rapid deterioration of brain function.2 Loss of life may occur within the first 10 years of life. Type II is the moderate, less severe form of the disease and involves a slower neurological breakdown that begins around 1.5 to 2 years of age.2 The mortality rate is similar to that of type one.

An individual's life expectancy is determined by the type of fucosidosis they have and the severity of the disease.

Type I fucosidosis clinical features

Features characteristic of type I fucosidosis may include the following:¹

• Enlargement of the liver, spleen or heart (i.e. hepatomegaly, splenomegaly and cardiomegaly, respectively)
• Coarsening of facial features
• Abnormal bone formation (i.e. dysostosis multiplex)
• Presence of cherry red spots on the retina of the eye
• Intellectual disability
• Seizures

Type II fucosidosis clinical features

Features characteristic of type II fucosidosis may include the following:¹

• Mild coarsening of facial features
• Abnormal bone formation (i.e., dysostosis multiplex)
• Intellectual disability
• Enlargement of the liver, spleen or heart (i.e., hepatomegaly, splenomegaly and cardiomegaly, respectively)
• Small wart-like lesions on the skin caused by dilated blood vessels (i.e. angiokeratomas)
• Malformed blood vessels in the eye membrane (i.e. vascular tortuosity)

Early-onset symptoms

Initial symptoms of fucosidosis may encompass mental defects and discoordination of motor function, such as delayed development of learning how to perform certain activities requiring muscular coordination (i.e. psychomotor retardation).³

Progressive neurological symptoms

Brain, or neurological, dysfunction may cause intellectual disability and difficulty in coordinating bodily movement, such as the inability to properly extend or rotate the limbs.³

Late stage symptoms

Severe fucosidosis might result in life-threatening complications to the brain and damage to nerve cells over time. This can affect memory, movement and other functions controlled by the brain (i.e. neurodegenerative complications). The person may even lose weight and muscle mass within the first few years of life.³

Other clinical features

Less common findings of fucosidosis that may occur in the late, severe stage of the disease include enlargement of organs such as the liver and spleen (i.e., hepatospleenomegaly) or the heart (i.e., cardiomegaly).³ The person may also experience seizures, hearing impairments, unusual curvature of the spine (known as kyphoscoliosis) and recurrent respiratory infections.³

Some people may experience involuntary movements of their muscles that affect the rigidity of limbs like the legs.³

FAQ’s

Is fucosidosis contagious?

No, fucosidosis is not a contagious disease. It is an inherited condition passed down in a family due to changes in a person’s genetic code, which is the blueprint of how we grow and develop.¹

Which type of fucosidosis is rare?

Type I fucosidosis is considered to be a rare disease in humans because many patients die a lot sooner in life, as compared to those with type II.⁴ People with type I fucosidosis cannot properly break down the sugar fucose, which results in severe neurological degeneration early in life.

Are there any disorders that have similar symptoms to fucosidosis?

Fucosidosis is a type of lysosomal storage disease, and there are around 50 of these that affect various parts of the body.³ Fabry disease is a rare inherited disorder that is characterised by the absence of the alpha-galactosidase enzyme, and symptoms may include the growth of wart-like lesions on the skin (i.e. angiokeratomas), which are also apparent in fucosidosis.³ Aspartylglucosaminuria is another rare genetic condition characterised by a deficiency in the activity or quantity of the enzyme aspartylglucosaminidase.³ This enzyme is essential for preventing the build-up of these compounds in the body, and some symptoms include intellectual disability, respiratory infections and coarsening of facial features.³

Is there a cure for fucosidosis?

There is currently no cure for fucosidosis.¹ The available treatment is often used to help manage symptoms.

Summary

Fucosidosis is a rare inherited disorder characterised by the abnormal build-up of sugar compounds, such as fucose, due to a deficiency of an essential enzyme known as alpha-L-fucosidase. The absence of this enzyme results in the build-up of sugar-containing material in lysosomes, and their eventual accumulation in various organs of the body, such as the liver, spleen or heart. Fucosidosis is considered an inherited disorder because the defective gene, FUCA1, must be passed down from both parents to bring about the disease. If an individual only inherits one faulty FUCA1 gene, they are considered a carrier, and they do not usually show signs or symptoms of the disease. There are two types of fucosidosis, and the severity of symptoms depends on the type a person has. In type I, which is the severe form, people may display a range of symptoms, such as abnormal bone formation, enlargement of internal organs, intellectual disability and seizures. In type II, the moderate (or less severe) form of the disease, people may present with mild coarsening of facial features, small lesions on the skin, twisted blood vessels and seizures. Other less common clinical features include abnormal curvature of the spine and hearing impairments.