Fucosidosis

Symptoms and signs

Symptoms are highly variable, with mild cases surviving into the third or fourth decade. Features include coarse facial features, enlarged liver, spleen, or heart, intellectual disability, seizures, abnormal bone formation, progressive deterioration of the brain and spinal cord, and altered perspiration. Severe cases (type 1) show rapid psychomotor regression, severe neurologic signs, elevated sweat sodium and chloride, and fatal outcome before age six.

Cause

Fucosidosis is an autosomal recessive disorder caused by mutations in the FUCA1 gene, which provides instructions for the alpha-L-fucosidase enzyme. This enzyme breaks down fucose-containing glycolipids and glycoproteins; its deficiency leads to lysosomal accumulation of these compounds. The buildup of partially broken down glycolipids and glycoproteins causes cell malfunction and death, especially in brain cells. Faulty degradation of both sphingolipids and polysaccharides occurs, and major accumulation of the H-antigen glycolipid is seen primarily in the liver.

Diagnosis

A special urine test checks for partially broken-down sugars; if present, a skin or blood sample is tested for below-normal alpha-fucosidase levels. The condition is autosomal recessive, meaning both parents must carry the mutation, with a 25% chance per child. Traditionally separated into types, fucosidosis is now considered a disease spectrum. Severe forms appear in the first 3 to 18 months, while milder forms appear between 12 and 24 months.

Did You Know?

• Research into bone marrow transplants to improve enzyme activity was ongoing as of 2023.
• Some researchers have speculated that blood type may play a role in the course of the disease.
• The disorder was first described in two Italian siblings who showed progressive intellectual disability and neurological deterioration.