Free Sialic Acid Storage Disorder

Excerpt

Clinical characteristics: Free sialic acid storage disorder (FSASD) is a spectrum of neurodegenerative phenotypes resulting from increased lysosomal storage of free sialic acid. Less severe FSASD (historically called Salla disease) is 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. Severe FSASD (historically referred to as infantile free sialic acid storage disease, or ISSD) is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.

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

Management: Treatment of manifestations: Management is symptomatic and supportive: standard treatment of seizures; developmental and educational support; rehabilitation to optimize mobility; supplementation of calcium and vitamin D for low bone density; feeding therapy and provision of adequate nutrition; treatment of ophthalmologic manifestations per ophthalmologist with low vision services as needed; treatment of cardiomegaly per cardiologist; treatment of nephropathy / nephrotic syndrome per nephrologist; surgical treatment of hernia as needed; family and social support.

Surveillance: Assessment of seizures, other neurologic manifestations, development, mobility, growth, nutrition, feeding, respiratory status, and family needs at each visit. Annual ophthalmology exam in those with intermediate or severe FSASD. Annual EKG and echocardiography to assess for cardiomegaly. Annual urinalysis for proteinuria.

Genetic counseling: FSASD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC17A5 pathogenic variant, each sib of an affected individual has at conception 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. Once the SLC17A5 pathogenic variants have been identified in an affected family member, molecular genetic carrier testing and prenatal/preimplantation genetic testing are possible.