Fucosidosis is a condition that affects many areas of the body, especially the brain. The symptoms of fucosidosis can vary from person to person. Affected individuals have intellectual disabilities that worsen with age. Over time, people with this condition tend to lose skills they had previously learned, such as sitting, standing, walking, or talking. Additional signs and symptoms of fucosidosis can include slow growth, abnormal bone development (dysostosis multiplex), and rigid or stiff muscles (spasticity). People with fucosidosis may also have clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) and distinctive facial features that are often described as "coarse." Additional features of fucosidosis can include frequent respiratory infections, an enlarged liver and spleen (hepatosplenomegaly), and seizures.

In the past, fucosidosis has been divided into two types based on the symptoms and age of onset. Type 1 was used to describe the more severe form of the disorder, with symptoms typically appearing in infancy. Type 2 was used to describe cases with milder symptoms and a slower progression. Currently, many researchers consider the condition to be a spectrum with a wide range in severity. 

Fucosidosis is a rare condition. As of 2023, fewer than 200 cases have been reported in the literature. The highest incidence of fucosidosis has been described in Italy, Cuba, and in certain populations of the Southwestern United States.

Variants (also called 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 sugar molecules (oligosaccharides) that are attached to certain fats (glycolipids) and proteins (glycoproteins). Alpha-L-fucosidase is responsible for cutting off (cleaving) a sugar molecule called fucose toward the end of the breakdown process.

FUCA1 gene variants severely reduce or eliminate the activity of the alpha-L-fucosidase enzyme. A loss of enzyme activity results in an incomplete breakdown of glycolipids and glycoproteins. These compounds gradually accumulate within various cells and tissues throughout the body. Brain cells are particularly sensitive to the buildup of glycolipids and glycoproteins. Damage to brain cells is thought to cause the neurological symptoms of fucosidosis. Glycolipids and glycoproteins also accumulate in other organs such as the liver, spleen, and skin.

Alpha-L-fucosidase is found in the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions like fucosidosis, that cause molecules to build up inside the lysosomes, are known as lysosomal storage disorders. 

Genetic Testing Information

• Genetic Testing Registry: Fucosidosis

Genetic and Rare Diseases Information Center

• Fucosidosis

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• FUCOSIDOSIS

Scientific Articles on PubMed

• PubMed

• Ben Turkia H, Tebib N, Azzouz H, Abdelmoula MS, Bouguila J, Sanhaji H, Miladi N, Maire I, Caillaud C, Kaabachi N, Ben Dridi MF. Phenotypic spectrum of fucosidosis in Tunisia. J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S313-6. doi: 10.1007/s10545-008-0891-0. Epub 2008 Jul 27. Citation on PubMed
• Bharati A, Higgins C, Ellis I, Wraith J. Fucosidosis: a therapeutic challenge. Pediatr Dermatol. 2007 Jul-Aug;24(4):442-3. doi: 10.1111/j.1525-1470.2007.00478.x. No abstract available. Citation on PubMed
• Cragg H, Williamson M, Young E, O'Brien J, Alhadeff J, Fang-Kircher S, Paschke E, Winchester B. Fucosidosis: genetic and biochemical analysis of eight cases. J Med Genet. 1997 Feb;34(2):105-10. doi: 10.1136/jmg.34.2.105. Citation on PubMed or Free article on PubMed Central
• Galluzzi P, Rufa A, Balestri P, Cerase A, Federico A. MR brain imaging of fucosidosis type I. AJNR Am J Neuroradiol. 2001 Apr;22(4):777-80. Citation on PubMed
• Kanitakis J, Allombert C, Doebelin B, Deroo-Berger MC, Grande S, Blanc S, Claudy A. Fucosidosis with angiokeratoma. Immunohistochemical & electronmicroscopic study of a new case and literature review. J Cutan Pathol. 2005 Aug;32(7):506-11. doi: 10.1111/j.0303-6987.2005.00366.x. Citation on PubMed
• Kaur A, Dhaliwal AS, Raynes H, Naidich TP, Kaufman DM. Diagnosis and Supportive Management of Fucosidosis: A Case Report. Cureus. 2019 Nov 12;11(11):e6139. doi: 10.7759/cureus.6139. Citation on PubMed
• Puente-Ruiz N, Ellis I, Bregu M, Chen C, Church HJ, Tylee KL, Gladston S, Hackett R, Oldham A, Virk S, Hendriksz C, Morris AAM, Jones SA, Stepien KM. Long-term outcomes in two adult siblings with Fucosidosis - Diagnostic odyssey and clinical manifestations. Mol Genet Metab Rep. 2023 Sep 27;37:101009. doi: 10.1016/j.ymgmr.2023.101009. eCollection 2023 Dec. Citation on PubMed
• Stepien KM, Ciara E, Jezela-Stanek A. Fucosidosis-Clinical Manifestation, Long-Term Outcomes, and Genetic Profile-Review and Case Series. Genes (Basel). 2020 Nov 22;11(11):1383. doi: 10.3390/genes11111383. Citation on PubMed
• Willems PJ, Gatti R, Darby JK, Romeo G, Durand P, Dumon JE, O'Brien JS. Fucosidosis revisited: a review of 77 patients. Am J Med Genet. 1991 Jan;38(1):111-31. doi: 10.1002/ajmg.1320380125. Citation on PubMed