Free Sialic Acid Storage Disorders

Clinical characteristics: Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.

Diagnosis/testing: The diagnosis of a FSASD is established in a proband by identification of biallelic pathogenic variants in SLC17A5 on molecular genetic testing.

Management: Treatment of manifestations: Management is symptomatic and supportive: standard treatment of seizures; feeding therapy and provision of adequate nutrition; rehabilitation to optimize mobility and communication; supplementation of calcium and vitamin D for low bone density; family and social support.

Surveillance: Assessment of feeding, respiratory status, seizures, development, mobility, and nutrition with each visit. Regular evaluation by a rehabilitation specialist to identify potentially helpful interventions. Annual EKG and echocardiography for cardiomegaly.

Genetic counseling: The FSASDs are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Molecular genetic carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the pathogenic variants in the family are known.