Free sialic acid storage disease E77.8

Free sialic acid lysosomal storage disease (FSASD) is an extremely rare, autosomal recessive, neurodegenerative multisystem disorder caused by defects in the lysosomal sialic acid membrane exporter SLC17A5 (sialin).

The disease is generally very rare (prevalence: <1 / 1 000 000), but in northern Finland about one in forty people is a heterozygous carrier of a mutation for SSD.

The cause is a mutation in the SLC17A5 gene, which is located on chromosome 6q14-q15. Several mutations have been described. After the enzymatic degradation of glycoproteins, glycosaminoglycans and glycolipids, the cleaved monosaccharides must be removed from the lysosome. The free sialic acids (synonym: acylneuraminic acids) are transported out of the lysosome via anion transporters. A defect in the anion transporter sialin leads to an accumulation of toxic sialic acid in the lysosome. The consequences in some cell types are enlarged lysosomes and a 10- to 100-fold increase in the excretion of free sialic acid in the urine (Huizing M et al. 2021).

The mean age at onset of the disease was 0.17 years. The mean age at diagnosis was 3 years with a mean diagnostic delay of 2.5 years.

The disease has different courses. Severe forms (ISSD: Infantile Sialic Acid Storage Disease) manifest prenatally with hydrops fetalis and ascites, or at birth with muscular hypotonia, hepatosplenomegaly, often associated with ascites, coarsened facial features, bone malformations, severe movement disorders, mental retardation and cerebral convulsions. These severe forms lead to death in early childhood.

The moderately severe forms (Salla syndrome), as described in Finland, manifest themselves in the first year of life with muscular hypotonia. As the disease progresses, spasticity, ataxia, psychomotor retardation and sometimes coarsened facial features are added. Most patients reach adulthood with severe mental retardation.

The laboratory diagnosis consists of the detection of increased excretion of free sialic acid in the urine and storage in fibroblasts, trophoblasts or amniotic cells. Only symptomatic treatment is possible.

There is no approved treatment for FSASD.

The median survival time was 11 years. The biochemical phenotype clearly predicted the course of the disease: patients with urinary excretion of free sialic acid below 6.37 times or intracellular storage of free sialic acid in fibroblasts below 7.37 times the normal value survived longer than patients with biochemical values above these thresholds (Zielonka M et al. 2019).

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5. Zielonka M et al. (2019) A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease-an ultra-orphan multisystemic lysosomal storage disorder. Genet Med 21:347-352