Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

• Published in: Molecular genetics and metabolism Vol. 82; no. 2; pp. 137 - 143
• Main Authors: Kleta, Robert, Morse, Richard P, Orvisky, Eduard, Krasnewich, Donna, Alroy, Joseph, Ucci, Angelo A, Bernardini, Isa, Wenger, David A, Gahl, William A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2004
• Subjects: Base Sequence; Brain - diagnostic imaging; Child, Preschool; DNA Mutational Analysis; Exons - genetics; Female; Fibroblasts; Humans; Infant; Infantile free sialic acid storage disease; ISSD; Lysosomal storage; Lysosomes - ultrastructure; Male; N-acetylneuraminic acid; N-Acetylneuraminic Acid - analysis; N-Acetylneuraminic Acid - urine; Organic Anion Transporters - genetics; Radionuclide Imaging; Salla disease; Sialic acid; Sialic Acid Storage Disease - diagnosis; Sialic Acid Storage Disease - genetics; Sialic Acid Storage Disease - metabolism; Sialic Acid Storage Disease - physiopathology; Skin - ultrastructure; Symporters - genetics; Lysosomal storage; ISSD; Sialic acid; Salla disease; Infantile free sialic acid storage disease; N-acetylneuraminic acid
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2004.03.001

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.