Novel form of intermediate salla disease: clinical and neuroimaging features.

The objective of this article is to describe the clinical, radiographic, and molecular genetic features of a new intermediate form of free sialic storage disease. Free sialic storage disease is a rare autosomal recessive lysosomal disorder that results from mutations in SLC17A5, a gene that codes for sialin, a lysosomal membrane sialic acid transporting protein. Infantile sialic acid storage disease has a severe phenotype, and Salla disease (Finnish variant) is generally milder in phenotype; intermediate forms have also been described. There have been few reports of magnetic resonance imaging (MRI) in the sialic acid storage disorders; leukodystrophy has been the characteristic finding, along with hypoplasia of the corpus callosum. An 8-month-old non-Finnish child presented with hypotonia and global developmental delay. Serial MRIs with magnetic resonance spectroscopy at 9 and 16 months revealed severe hypomyelination and hypogenesis of the corpus callosum. There was mild elevation of urinary sialic acid (4.5 times above normal). Electron microscopy of a skin biopsy showed lysosomal enlargement with oligosaccharide storage, and confirmatory molecular genetic testing revealed compound heterozygosity for two new SLC17A5 mutations. Free sialic storage disease of the intermediate type is an important part of the differential diagnosis of a hypotonic, delayed child with abnormal white matter on MRI. Intermediate types of free sialic acid overlap in phenotype with infantile sialic acid storage disease and the milder Salla disease and thus might be more difficult to identify clinically; the lack of Finnish ethnicity should not preclude testing for this probably under-recognized disorder. White-matter abnormalities appear to be characteristic of the entire phenotypic spectrum.