Sialic Acid Storage Disease

Sialic acid storage disease is a rare, inherited disorder that predominantly affects the central nervous system. The symptoms associated with the disease are highly variable between individuals affected, with a broad spectrum of disease severity. These differences in symptoms and presentation have led to three separate classifications of the disorder: infantile free sialic acid storage disease (ISSD), Salla disease, and intermediate severe Salla disease. Sialic acid storage disease is one of about 50 separate diseases which are classified as lysosomal storage disorders (LSD).

Lysosomes in human cells contain specific proteins known as enzymes which are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes, or do not contain one of these enzymes in sufficient quantities to break down molecules in the way we would expect for proper cellular function.

Manifestations of sialic acid storage disease can vary significantly depending on the subtype of the disease a child has. Features of infantile free sialic acid storage disease (ISSD) appear immediately or shortly after birth and progress more rapidly than symptoms in other subtypes. Children diagnosed with Salla disease or intermediate severe Salla disease typically develop symptoms in the first year of life.

Signs and symptoms include:

• Poor muscle tone (hypotonia)
• Enlarged organs (organomegaly)
• Failure to gain weight and length (failure to thrive)
• Distinct facial features (coarse facial features)
• Seizures
• Intellectual disability
• Bone malformations
• Difficulty with movement and balance (ataxia)
• Abnormal tensing of muscles (spasticity)
• Involuntary writhing movements of the limbs (athetosis)

In all three subtypes of sialic acid storage disease, a genetic variation in the gene known as SLC17A5 results in the dysfunction of a specialized protein known as sialin. Sialin is located in the lysosomes of cells. Under normal conditions, this protein helps to remove sialic acid produced during the breakdown of certain fats and proteins from the lysosomes and transport it to other parts of the cell. In individuals with sialic acid storage disease, dysfunctional sialin prevents the removal of sialic acid from the lysosomes, resulting in an abnormal accumulation of the substance which eventually causes signs and symptoms of disease.

Sialic acid storage disease is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the SLC17A5 gene from each of their parents.

There are currently no approved therapies to reverse the effects of any subtype of multiple sialic acid storage disease. Current approaches to sialic acid storage disease involve interdisciplinary collaboration to provide supportive therapies and targeted management for specific symptoms.

At the Boston Children’s Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with sialic acid storage disease.