Case Report: A rare case of fucosidosis caused by a novel homozygous pathogenic variant in the FUCA1 gene within a 17.2 Mb region of homozygosity.

Fucosidosis is a rare lysosomal storage disorder caused by mutations in the FUCA1 gene, leading to deficient α-L-fucosidase activity and the accumulation of fucosylated substrates. The clinical spectrum varies widely, encompassing neurological regression, coarse facial features, angiokeratomas, hepatosplenomegaly, and systemic involvement. Here, we report a case of fucosidosis in a patient presenting with prominent progressive neurological symptoms and atypical angiokeratoma-like skin lesions, but notably absent hepatosplenomegaly or cardiac involvement. Additional features included recurrent respiratory illnesses. Genetic analysis identified a novel homozygous nonsense mutation, c.557 T > A (p.Leu186*), in the FUCA1 gene located within a 17.2 Mb region of homozygosity at 1p36.21p35.2. This variant truncates the catalytic domain and expands the FUCA1 mutation spectrum. The case highlights the disorder's phenotypic heterogeneity and the importance of early genetic diagnosis to enable timely interventions such as hematopoietic stem cell transplantation (HSCT).