Salla disease, also known as Salla leukoencephalopathy or sialic acid storage disease, is a rare genetic disorder primarily affecting the nervous system. It falls under the category of lysosomal storage diseases. Salla disease is characterized by the abnormal accumulation of sialic acid in the cells due to a deficiency of a specific transporter protein. The incidence of Salla disease worldwide is approximately one case per million people.
Salla disease genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
The key features and aspects of Salla disease are:
- Genetic Cause: Salla disease is an autosomal recessive disorder, meaning an individual must inherit two copies of the mutated gene (SLC17A5) — one from each parent — to develop the condition. The SLC17A5 gene provides instructions for producing a protein involved in sialic acid transport across cell membranes.
- Accumulation of Sialic Acid: The lack of functional transporter protein leads to the accumulation of sialic acid within the lysosomes of cells. Lysosomes are cellular compartments responsible for breaking down and recycling various substances. The abnormal buildup of sialic acid can disrupt normal cellular function, particularly in the nervous system.
- Neurological Symptoms: The primary manifestations of Salla disease are neurological. Individuals with the condition may experience hypotonia (weak muscle tone), ataxia (lack of coordination), delayed motor skills, and intellectual disabilities. The severity of symptoms can vary.
- Language and Speech Impairments: Some individuals with Salla disease may have language and speech difficulties, including delayed speech development and articulation problems.
- Diagnosis: Salla disease is typically diagnosed through genetic testing, which identifies mutations in the SLC17A5 gene. Additionally, laboratory tests may reveal elevated levels of sialic acid in urine.
- Treatment and Management: Salla disease has no cure. Treatment is generally supportive and aims to manage symptoms. Physical and occupational therapy may be beneficial for addressing motor skills and improving quality of life.
Salla disease follows an autosomal recessive mode of inheritance. It occurs when a person inherits one copy of the mutated gene from each parent, and the parents are carriers without having the disease. Therefore, affected individuals will have two copies of a pathogenic mutation. As we have indicated, the gene involved in Salla disease is SLC17A5; to date, more than 55 pathogenic variants have been described. Cases of patients with two distinct mutations in SLC17A5 in compound heterozygosity have also been reported.
The c.115C>T (p.Arg39Cys) variant is a Finnish founder pathogenic variant identified in most cases of Salla patients. Functional studies have shown that c.115C>T reduces sialic acid transport across the lysosomal membrane. Homozygotes for c.115C>T do not have the most severe form of the disease but suffer mainly from progressive cognitive impairment. When this variant is present in compound heterozygosity with another pathogenic variant, it produces a disease of intermediate severity.
The c.406A>G (p.Lys136Glu) mutation is another variant usually present in Salla patients worldwide and produces disease of intermediate severity when present in homozygosity. This mutation markedly reduces the enzymatic activity of the lysosomal transporter encoded by SLC17A5. It has been shown that c.406A>G may be in compound heterozygosity with other pathogenic variants of SLC17A5 in Salla patients.
Salla disease genetic testing analyzes the three most frequent pathogenic mutations of the SLC17A5 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
