Fucosidosis

Other Names: Alpha-l-fucosidase deficiency; Lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues

Fucosidosis is a lysosomal storage disease that affects many areas of the body, especially the brain.

In the past, researchers described two types of this condition based on symptoms and age of onset, but current opinion is that the two types are actually a single disorder with signs and symptoms that range in severity.

Onset

In severe cases, symptoms typically appear in infancy, and affected individuals usually live into late childhood. In milder cases, symptoms begin at age 1 or 2, and affected individuals tend to survive into mid-adulthood.

Epidemiology

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.

Cause

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Affected individuals have intellectual disability that worsens with age, and many develop dementia later in life. People with this condition often have delayed development of motor skills such as walking; the skills they do acquire deteriorate over time.

Additional signs and symptoms of fucosidosis include impaired growth; abnormal bone development (dysostosis multiplex); seizures; abnormal muscle stiffness (spasticity); clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas); distinctive facial features that are often described as "coarse"; recurrent respiratory infections; and abnormally large abdominal organs (visceromegaly).

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Anterior beaking of lumbar vertebrae
• Brachycephaly(Short and broad skull)
• Coarse facial features(Coarse facial appearance)
• Dysostosis multiplex
• Failure to thrive(Faltering weight)
• Generalized hyperkeratosis
• Global developmental delay
• Hearing impairment(Deafness)
• Hepatomegaly(Enlarged liver)
• Hyperhidrosis(Excessive sweating)
• Hypothyroidism(Underactive thyroid)
• Intellectual disability, severe(Early and severe mental retardation)
• Kyphosis(Hunched back)
• Lipoatrophy(Loss of fat tissue in localized area)
• Mucopolysacchariduria
• Prominent forehead(Pronounced forehead)

30%-79% of people have these symptoms

• Abnormality of the gallbladder
• Corneal opacity
• Decreased muscle mass
• Muscular hypotonia(Low or weak muscle tone)
• Seizure
• Spastic tetraplegia
• Vascular skin abnormality

5%-29% of people have these symptoms

• Abnormal pyramidal sign
• Abnormality of the dentition(Abnormal dentition)
• Abnormality of the nail
• Acrocyanosis(Persistent blue color of hands, feet, or parts of face)
• Cardiomegaly(Enlarged heart)

Diagnosis

A special urine test is available to check for any partially broken-down-sugars. If they are present, a skin or blood sample will be taken to test for below-normal amounts of alpha-fucosidase.

Molecular Genetics Tests:

• Deletion/duplication analysis
• Sequence analysis of the entire coding region
• Targeted variant analysis
• Sequence analysis of select exons

Treatment

• There is no treatment or way to reverse the disease. Treatment will focus on the symptoms an individual has, such as seizure medication.
• It is possible that if an individual receives a bone marrow transplant, they could receive healthy bone marrow cells which would produce normal amounts of fucosidase. But there not is enough research to prove this is an effective treatment.

NIH genetic and rare disease info

• NIH info on Fucosidosis

Fucosidosis is a rare disease.

Fucosidosis Resources
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