Overview

Can you imagine a tiny molecule of sugar playing an important role in keeping your body functioning properly? This sugar is called fucose and your body needs it to do certain activities. But what happens if your body cannot break the compounds containing fucose? The result will be a build-up of these compounds in tissues leading to so-called fucosidosis.¹

This condition happens when the enzyme alpha-L-fucosidase (which metabolizes compounds containing fucose sugar) fails to function, causing this inherited disease, a lysosomal storage disease with an autosomal recessive nature.^1,2

Affected populations

Fucosidosis can be present in males and females at the same frequency. Fewer than one hundred cases have been documented in the literature. According to one estimate, the incidence rate is fewer than 1 in 200,000 live births. Some researchers argue that the true number of the affected population is challenging to ascertain because the disease is not sufficiently diagnosed (underdiagnosed).¹

Types of fucosidosis

Typically, there are two main types of fucosidosis. However, researchers now believe it resembles a disease range, with the severe form (referred to as fucosidosis type I) at one extreme and the mild form (referred to as fucosidosis type II) at the other.¹

It is not known yet why individuals with fucosidosis have a variety of intensities and signs.¹ Some researchers argue that the genetic abnormality in the FUCA1 gene alongside other determinants related to genes and environment can affect the severity of fucosidosis in patients.¹

Type I fucosidosis

The severe form of the disease is characterized by a fast progression and early onset.¹ Typically appears within the age of 3 to 18 months.³ It is also called Fucosidosis Severe, Fucosidosis Infantile Type, Alpha-L-Fucosidase Deficiency, and ALF.⁴

Neurological symptoms

Neurological symptoms may happen due to ongoing neurological damage including cognitive delay, movement impairment, and brain-related stiffness (decerebrate rigidity), characterized by rigid extensions and rotations of the limbs that happen uncontrollably.¹

Physical characteristics

Physical change may also occur including rough facial characteristics and enlarged tongue and lips, patients can also have abnormalities in bones and muscles like mild dysostosis multiplex, and hypotonia (weekend muscles) resulting in muscle softness and delay in growth.¹

Organ involvement

Organs may increase in size (visceromegaly or organomegaly) including the spleen and liver known as hepatosplenomegaly or the heart known as cardiomegaly.^1,3 

Red spots on the retina may appear, causing the rest of the healthy retina to look bright.³

Other symptoms

Other symptoms include seizures, spinal malformation (kyphoscoliosis), respiratory infections, and loss of hearing, some people might overly sweat, and the sweat may hold a high concentration of salt or chlorine.^1,3 

Progression and prognosis

Rapid progression of neurological symptoms leads to early death in childhood, usually between the ages of 5 and 10 years, the death generally happens because of cachexia (extreme weight loss).^5,6

Type II fucosidosis

The less severe form of the disease is characterized by a slower progression and milder symptoms.¹ Typically emerges between 1 and 2 years of age.³

Neurological symptoms

Neurological symptoms might not become noticeable until a child is between 18 months and 3 years old.¹ cognitive delay may appear.³

Physical characteristics

Rough facial characteristics are present but less obvious than the severe type.³ skeletal abnormalities may also be present like dysostosis multiplex.²

Other features are angiokeratomas (growths that look like warts on the skin above surface widened blood vessels), which start to appear at 2 years of age.^1,3 In addition to abnormal blood vessel shape in the eyes.³

Organ involvement

In this form of the disease, organs may also increase in size (organomegaly) including the spleen and liver. Cardiac symptoms may also be involved.³

Other symptoms

Some individuals may experience contractures meaning that some joints are always flexed, they also may experience hardships in moving their legs due to spasticity (uncontrolled muscle contractions), in addition to anhidrosis (insufficient sweat capability).¹

Progression and prognosis

People with this type of fucosidosis may make it to their 2^nd 3^rd or even 4^th decades before getting serious issues that can lead to their death due to slower development of neurological symptoms, on the other hand, most of them experience angiokeratoma corporis diffusum.^1,5

Underlying Cause

The enzyme alpha-L-fucosidase is generated based on the instructions from a gene known as FUCA1. When a change occurs in this gene, fucosidosis disease appears. As a result of the alpha-L-fucosidase enzyme failing to function properly, the cells also fail to perform their normal function due to excess build-up of sugar compounds in them.⁷

To date, it has not been proven that there is a link between the location of the disease-causing mutation in the FUCA1 gene and the level of symptom severity.⁶

Inheritance

A person has to receive two copies of the faulty FUCA1 gene, one from each parent to get the disease, that is why fucosidosis disease follows an autosomal recessive pattern.⁷

People with fucosidosis disease have a pseudogene called FUCAP1 that cannot produce proteins or is not expressed in the body anymore.¹

A person can carry the disease with no symptoms if they inherit only one defective gene of the disease.¹

For each pregnancy between two carriers of fucosidosis, there is a 25% chance of having a child with fucosidosis, a 50% chance of having a child who is a carrier of the disease, and a 25% chance of having a child with normal genes. The chances are the same for males and females.¹

Diagnosis

• Initial suspicion: Typically, in infants with skeletal and neurological symptoms within the first year of their lives. It is confirmed through clinical examination and tests alongside patient history¹
• Tissue examination: Abnormal cell vacuoles (cavities) are observed via electron microscopy in tissues like the liver, skin, spleen, etc¹
• Advanced imaging: MRI (magnetic resonance imaging) and CT (computer-assisted tomography) scans can reveal brain white matter degeneration¹
• Urine analysis: Elevated fucose-containing compounds can indicate the disease¹
• Enzyme activity tests: Reduced alpha-L-fucosidase activity can be detected through enzyme tests¹
• Prenatal/ Antenatal diagnosis: Fucosidosis can be diagnosed before birth using specialized tests like chorionic villus sampling (CVS) or amniocentesis^1,6
• Genetec testing: to confirm the diagnosis⁶
• Differential diagnosis: Other lysosomal storage diseases can be excluded through genetic and biomedical tests and clinical evaluation⁶

 Ultimately, the diagnosis of fucosidosis involves clinical symptoms, and biochemical tests showing increased fucosylated oligosaccharides in urine and reduced α-L-fucosidase activity in blood, with confirmation through genetic testing.⁶

Treatment

There is no cure for fucosidosis and treatment focuses on managing symptoms for each patient.^1,3 Common approaches include antibiotics for respiratory infections and fluid replacement for dehydration caused by heavy sweating.^1,6 Genetic counseling is recommended for those with the disease and their families.¹ Supportive care is key, and early diagnosis with ongoing care can improve the quality of life and potentially extend the survival of individuals with the disease.⁶

Bone marrow transplantation performed before severe symptoms appear may be effective, but long-term outcomes remain uncertain.⁶ 

Simplifying the differentiation between type I and type II fucosidosis

Summary

Fucosidosis is an uncommon genetic condition resulting from a lack of the enzyme alpha-L-fucosidase. It has two main forms: Type I, which is severe with early onset and rapid progression, and Type II, which is milder with later onset and slower progression. Diagnosis involves clinical evaluation, biochemical tests, and genetic analysis. Treatment involves addressing symptoms and offering supportive care, as no cure exists. Further research is needed to understand the factors influencing the severity and type of fucosidosis.