Biochemical and molecular analyses of infantile free sialic acid storage disease in North American children

Am J Med Genet A. 2003 Jul 1;120A(1):28-33. doi: 10.1002/ajmg.a.20024.


The differential diagnosis of developmental delays and growth retardation in early childhood includes the allelic lysosomal sialic acid storage disorders, Salla disease and infantile free sialic acid storage disease (ISSD). These diseases, due to defective free sialic acid transport out of lysosomes, derive from mutations in the SLC17A5 gene coding for the protein sialin. We present two patients with clinical, biochemical, and molecular data indicative of lysosomal free sialic acid storage disorders. One patient, with a severe clinical course typical of ISSD, had 86-fold elevated levels of fibroblast free sialic acid, with 62% in the lysosomal fraction. His SLC17A5 mutations include a 148-bp deletion of exon 9, due to a G >A splice site mutation in position 1 of intron 9, and a 15-bp deletion (del 801-815) in exon 6. Another patient, with "intermediate severe" Salla disease, had 9-fold elevated levels of free sialic acid in cultured fibroblasts, of which 87% resided in the lysosomal fraction. This girl is compound heterozygous for the SLC17A5 mutation commonly found in Finnish Salla disease patients (R39C) and a 15-bp deletion found in ISSD patients (del 801-815). These observations emphasize the importance of considering free sialic acid disorders in infants with developmental delays and growth retardation, regardless of whether they are of Finnish ancestry.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Exons
  • Facies
  • Female
  • Fibroblasts / metabolism
  • Heterozygote
  • Humans
  • Infant
  • Introns
  • Lysosomes / metabolism
  • Male
  • Molecular Sequence Data
  • Mutation
  • N-Acetylneuraminic Acid / metabolism
  • Organic Anion Transporters / genetics
  • Polymerase Chain Reaction
  • Sialic Acid Storage Disease / genetics*
  • Sialic Acid Storage Disease / metabolism*
  • Subcellular Fractions
  • Symporters / genetics


  • Organic Anion Transporters
  • Symporters
  • sialic acid transport proteins
  • N-Acetylneuraminic Acid