Fucosidosis

Fucosidosis (also known as alpha-fucosidase deficiency) is a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-L-fucosidase, which is responsible for breaking down fucose-containing glycolipids, glycoproteins, and oligosaccharides. The accumulation of these undegraded substrates in tissues throughout the body leads to progressive multisystem damage. The disease is caused by pathogenic variants in the FUCA1 gene located on chromosome 1p36.11. Fucosidosis has historically been classified into two clinical subtypes, though they represent a continuum of severity. Type 1 (severe form) presents in infancy with rapid psychomotor regression, severe neurological deterioration, growth retardation, coarse facial features, hepatosplenomegaly, recurrent respiratory infections, and dysostosis multiplex (skeletal abnormalities). Death typically occurs in the first decade of life. Type 2 (milder form) has a slower progression, with patients surviving into the second or third decade. Distinctive features of type 2 include angiokeratomas (clusters of dark red skin lesions), which are less common in the severe form. Both types involve progressive intellectual disability, seizures, and motor dysfunction. The central nervous system, skeletal system, skin, liver, spleen, and heart can all be affected. Elevated sweat chloride levels may also be observed, which can initially suggest cystic fibrosis. There is currently no approved specific therapy for fucosidosis. Management is primarily supportive and symptomatic, including physical therapy, seizure management, and treatment of infections. Hematopoietic stem cell transplantation (HSCT) has been attempted in a limited number of cases with variable outcomes, showing some stabilization of symptoms when performed early in the disease course. Enzyme replacement therapy and gene therapy remain areas of research but are not yet clinically available.

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