title: Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity.
abstract: The allelic autosomal recessive lysosomal storage disorders Salla disease and infantile free sialic acid storage disease (ISSD) result from mutations in SLC17A5. This gene codes for sialin, a lysosomal membrane protein that transports the charged sugar, N-acetylneuraminic acid (sialic acid), out of lysosomes. ISSD has a severe phenotype with infantile onset, while the Finnish variant, Salla disease, has a milder phenotype with later onset. Both disorders cause developmental delay, and ISSD is generally fatal in early childhood. We describe a 30-month old non-Finnish, Caucasian child with global developmental delay of postnatal onset, language, and motor skills stagnant at a 3-4 month level, hypotonia, and mild but progressive coarsening of facial features. Urinary excretion of free sialic acid was elevated 4.5 times above control. EM of a skin biopsy revealed enlarged secondary lysosomes consistent with oligosaccharide storage. Free sialic acid in fibroblasts was 3.8+/-0.9 nmol/mg protein (concurrent normal controls, 0.5+/-0.1); differential centrifugation indicated a lysosomal location. Genomic analysis revealed compound heterozygosity for two new SLC17A5 mutations. This child's clinical manifestations of a lysosomal free sialic acid storage disease are consistent with her sialin mutations and biochemical findings. The differential diagnosis of postnatal developmental delay should include free sialic acid storage disorders such as ISSD and Salla disease.
authors.affiliation: Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. kletar@mail.nih.gov
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Richard P
authors.initials: RP
authors.lastname: Morse
authors.forename: Eduard
authors.initials: E
authors.lastname: Orvisky
authors.forename: Donna
authors.initials: D
authors.lastname: Krasnewich
authors.forename: Joseph
authors.initials: J
authors.lastname: Alroy
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Ucci
authors.forename: Isa
authors.initials: I
authors.lastname: Bernardini
authors.forename: David A
authors.initials: DA
authors.lastname: Wenger
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000000981:diagnostic imaging; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000032:analysis / Q000652:urine; D027361:Organic Anion Transporters / Q000235:genetics; D011877:Radionuclide Imaging; D029461:Sialic Acid Storage Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D012867:Skin / Q000648:ultrastructure; D027981:Symporters / Q000235:genetics
chemical_list: D027361:Organic Anion Transporters; D027981:Symporters; C421224:sialic acid transport proteins; D019158:N-Acetylneuraminic Acid