Galactosialidosis

Galactosialidosis (also known as Goldberg syndrome, neuraminidase deficiency with beta-galactosidase deficiency, or combined neuraminidase and beta-galactosidase deficiency) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTSA gene, which encodes the protective protein/cathepsin A (PPCA). This protein is essential for stabilizing and protecting the lysosomal enzymes neuraminidase 1 (sialidase) and beta-galactosidase. When PPCA is deficient or dysfunctional, both of these enzymes are rapidly degraded, leading to the accumulation of sialyloligosaccharides and other substrates within lysosomes throughout the body. Three clinical forms are recognized: an early infantile (severe) form, a late infantile form, and a juvenile/adult form. The early infantile form presents with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile form features hepatosplenomegaly, growth retardation, cardiac involvement, and skeletal abnormalities. The juvenile/adult form, which is the most common and is particularly prevalent in Japan, is characterized by progressive neurological deterioration, cerebellar ataxia, myoclonus, seizures, intellectual disability, cherry-red macular spots, corneal clouding, coarse facial features, dysostosis multiplex, angiokeratomas, and hearing loss. Visceromegaly is generally less prominent in the juvenile/adult form. There is currently no curative treatment for galactosialidosis. Management is supportive and symptomatic, addressing seizures, cardiac complications, orthopedic issues, and visual or hearing impairment. Bone marrow transplantation has been explored in some cases with limited success. Research into enzyme replacement therapy and gene therapy is ongoing but remains experimental. Diagnosis is confirmed by demonstrating combined deficiency of neuraminidase and beta-galactosidase in fibroblasts or leukocytes, and by molecular analysis of the CTSA gene.

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