Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease.

Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.

Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood.

People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity.

Mutations in the SLC17A5 gene cause all forms of sialic acid storage disease. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves a molecule called free sialic acid, which is produced when certain proteins and fats are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules. Researchers believe that sialin may also have other functions in brain cells, in addition to those associated with the lysosomes, but these additional functions are not well understood.

Approximately 20 mutations that cause sialic acid storage disease have been identified in the SLC17A5 gene. Some of these mutations result in sialin that does not function normally; others prevent sialin from being produced. In a few cases, sialin is produced but not routed properly to the lysosomal membrane.

SLC17A5 gene mutations that reduce or eliminate sialin activity result in a buildup of free sialic acid in the lysosomes. It is not known how this buildup, or the disruption of other possible functions of sialin in the brain, causes the specific signs and symptoms of sialic acid storage disease.

Normal Function

The SLC17A5 gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves a molecule called free sialic acid, which is produced when certain proteins and fats are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules.

Researchers believe that sialin may also have other functions in brain cells, in addition to those associated with the lysosomes, but these additional functions are not well understood.

Health Conditions Related to Genetic Changes

Sialic acid storage disease

Approximately 20 mutations that cause sialic acid storage disease have been identified in the SLC17A5 gene. Some of these mutations result in sialin that does not function normally; others prevent sialin from being produced. In a few cases, sialin is produced but not routed properly to the lysosomal membrane.

There are three forms of sialic acid storage disease. A particular SLC17A5 mutation, found primarily in people from Finland and Sweden, causes the least severe form of this disorder known as Salla disease. This mutation replaces the protein building block (amino acid) arginine with the amino acid cysteine at position 39 of the sialin protein (written as Arg39Cys or R39C). Other SLC17A5 gene mutations that have more damaging effects on sialin protein function cause the most severe form of the disorder, infantile free sialic acid storage disease. Individuals diagnosed with intermediate severe Salla disease have one copy of the SLC17A5 gene with the Salla disease mutation in each cell, while the second copy of the gene bears a more severe mutation. The severity of signs and symptoms of intermediate severe Salla disease falls between those of Salla disease and infantile free sialic acid storage disease.

SLC17A5 gene mutations that reduce or eliminate sialin activity result in a buildup of free sialic acid in the lysosomes. It is not known how this buildup, or disruption of other possible functions of sialin in the brain, causes the specific signs and symptoms of sialic acid storage disease.

Other Names for This Gene

• AST
• ISSD
• NSD
• S17A5_HUMAN
• SD
• SIALIN
• SIASD
• SLD
• solute carrier family 17 (acidic sugar transporter), member 5
• solute carrier family 17, member 5

Genomic Location

Free sialic acid storage diseases are inherited in an autosomal recessive pattern. All individuals inherit two copies of each gene. To have a free sialic acid storage disease, a person must have a mutation in both copies of the SLC17A5 gene in each cell. There is nothing either parent can do, before or during pregnancy, to cause a child to have this.

People with autosomal recessive conditions inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

• 25% (1 in 4) chance to have the disorder
• 50% (1 in 2) chance to be an unaffected carrier like each parent
• 25% (1 in 4) chance to be unaffected and not be a carrier

Sialic acid storage disease is a very rare disorder. ISSD has been identified in only a few dozen infants worldwide. Salla disease occurs mainly in Finland and Sweden and has been reported in approximately 150 people. A few individuals have been identified as having intermediate severe Salla disease.