Abstracts

Rationale: Salla disease (SD) and infantile free sialic acid storage disease (ISSD) are recessively inherited, neuro-degenerative disorders caused by mutations in the SLC17A5 gene. SLC17A5 encodes a lysosomal membrane protein, sialin, which transports sialic acid from lysosomes. In the CNS, sialin is predominantly expressed in neurons, especially in the proliferative zone of the prospective neocortex and the hippocampus in developing brain. The effects of disordered sialic acid storage on the CNS are numerous, and include severe developmental delay, regression, and seizures. Sialic acid storage disorders have been variably associated with epilepsy. Seizures are mentioned in the literature, but there have been no reports of the kind of epilepsy that these children experience. There is a wide phenotypic spectrum described in sialic acid storage disorders, the commonest being Salla disease, which occurs predominantly in the Finnish population and is the most mild clinically, compatible with long survival and infrequently having epilepsy. ISSD is the most severe phenotype and is associated with limited survival; seizures have been described in this disorder but have not been well characterized. Intermediate severe salla disease (ISD) is quite rare, occurring sporadically, and there are no long term reports available regarding these children, particularly in regards to epilepsy. We have followed a patient with molecular genetically confirmed ISD for 15 years, beginning at 8 months, and have serial EEGs, MRIs, and examinations which document her clinical course. Genomic analysis revealed compound heterozygosity for two new SLC17A5 mutations. The epilepsy began with febrile seizures but as she regressed, afebrile and then reflex seizures (startle audiogenic seizures) appeared and became medically resistant. A detailed description of the epilepsy associated with ISD provide the basis of this report.Methods: We reviewed the literature about disorders of sialic acid storage to determine what had been published about epilepsy and EEG characteristics in disorders of sialic acid storage, with a special interest in ISD. We extracted serial EEG, MRI reports, and history/examination data to document the clinical course/evolution of our patient.Results: see tableConclusions: Epilepsy has not been characterized in ISD, a rare neurometabolic disorder associated with developmental regression. Our patient developed epilepsy over time, going from fever-associated seizures as a young child with a relatively normal EEG, to afebrile seizures, to spontaneous intermittent seizures and frequent reflex seizures, medically resistant. Unlike the more common Salla disease, ISD appears to carry a high risk of seizures (and most likely an increased risk of SUDEP, due to the longer survival of these children than the severe infantile form). Sialic acid storage should be considered in the differential diagnosis of symptomatic epilepsy of childhood associated with unexplained developmental delay or regression and delayed myelination on MRI.