Sialic acid storage disease

Rare autosomal recessive inherited lysosomal storage disease.

A distinction is made between 2 forms:

• Type 1: Adult form (Salla disease)
• Type 2: Infantile sialic acid storage disease (ISSD)

Maturity incidence of the infantile form: 1/ 500.000 births.

mutation of the SLC17A5 gene (chromosome 6 gene locus q14-q15). The gene codes for the protein sialin, an anion/sugar transporter, which is preferably concentrated in the membrane of lysosomes. Mutations in the SLC17A5 gene lead to sialin that is disturbed in its function.

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 removed from the lysosome by anion transporters. A defect in the anion transporter sialin leads to an accumulation of toxic sialic acid in the lysosome.

Infantile form: rough facial features, hepatosplenomegaly, ataxia, mental retardation; dysostosis multiplex (Mohammad An 2018). The prognosis of the infantile form is extremely unfavourable. The affected children usually die within the first years of life.

Adult form (Salla disease): First symptoms in infancy. Hypotension with/without horizontal nystagmus. Later spasticity. Mental retardation. No speech ability. Most patients reach adulthood.

No causal therapy known. The treatment is symptomatic.

1. Leppanen P et al (1996) A physical map of the 6q14-q15 region harboring the locus for the lysosomal membrane sialic acid transport defect. Genomics 37: 62-67.
2. Mohammad AN et al (2018) Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement. Mol Genet Metab Rep 15:11-14.
3. Verheijen FW et al (1999) A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. Nature Gene 23: 462-465.
4. Zielonka M et al(2018) A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease-an ultra-orphan multisystemic lysosomal storage disorder. Genet Med doi: 10.1038/s41436-018-0051-3.