title: Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics.
abstract: Sialuria, a disorder of sialic acid (NeuAc) metabolism characterized by increased free NeuAc in the cytoplasm of cells, is due to failure of CMP-Neu5Ac to feedback inhibit UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We now describe the fifth patient in the world with sialuria, a 7-year-old Portuguese girl with developmental delay, hepatomegaly, coarse facies, and urinary excretion of 19 micromol of free NeuAc/mg creatinine. The patient's fibroblasts stored excess free NeuAc in the cytosolic fraction, and fibroblast UDP-GlcNAc 2-epimerase activity was only 26% inhibited by 100 microM CMP-Neu5Ac (normal, 79%). The patient's UDP-GlcNAc 2-epimerase gene displayed an R266Q mutation in only one allele, consistent with known sialuria mutations and with the proposed dominant nature of this disorder. Extensive description of sialuria patients will help to define the clinical and biochemical spectrum of this disease.
authors.affiliation: Departamento de Pediatria, Hospital Maria Pia, Porto, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Ferreira
authors.forename: R
authors.initials: R
authors.lastname: Seppala
authors.forename: R
authors.initials: R
authors.lastname: Pinto
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: E
authors.initials: E
authors.lastname: Martins
authors.forename: A C
authors.initials: AC
authors.lastname: Braga
authors.forename: L
authors.initials: L
authors.lastname: Gomes
authors.forename: D M
authors.initials: DM
authors.lastname: Krasnewich
authors.forename: M C
authors.initials: MC
authors.lastname: Sa Miranda
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics; D002238:Carbohydrate Epimerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000494:pharmacology; D029968:Escherichia coli Proteins; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000652:urine; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D017354:Point Mutation; D012794:Sialic Acids / Q000378:metabolism / Q000652:urine*; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D012794:Sialic Acids; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C083982:wecB protein, E coli; D019158:N-Acetylneuraminic Acid