Free sialic acid storage disease

Free sialic acid storage disease (FSASD) is a group of rare autosomal recessive lysosomal storage disorders caused by mutations in the SLC17A5 gene, which encodes sialin, a lysosomal membrane transporter responsible for exporting free sialic acid (N-acetylneuraminic acid) out of lysosomes. When this transporter is defective, free sialic acid accumulates within lysosomes, leading to progressive cellular damage. The disease spectrum includes two main clinical forms: Salla disease (the milder form, also known as Finnish type sialuria) and infantile free sialic acid storage disease (ISSD), the severe form. An intermediate phenotype also exists. Infantile free sialic acid storage disease (ISSD) presents at birth or in early infancy with severe features including hydrops fetalis, hepatosplenomegaly, coarse facial features, severe intellectual disability, failure to thrive, skeletal dysplasia, and nephrotic syndrome. Most affected infants die within the first two years of life. Salla disease, named after a municipality in Finnish Lapland where it was first described, has a later onset and milder course. Children with Salla disease typically present with hypotonia, ataxia, progressive psychomotor delay, intellectual disability, and spasticity. Nystagmus and seizures may also occur. Affected individuals with Salla disease may survive into adulthood but with significant neurological impairment. The disease primarily affects the central nervous system, liver, spleen, kidneys, and skeletal system. Diagnosis is confirmed by elevated free sialic acid levels in urine and fibroblasts, and by molecular genetic testing of the SLC17A5 gene. Brain MRI typically shows hypomyelination and corpus callosum abnormalities. There is currently no curative treatment for free sialic acid storage disease. Management is supportive and symptomatic, including physical therapy, occupational therapy, seizure management, and nutritional support. Hematopoietic stem cell transplantation has been attempted in severe cases but with limited success.

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