title: New observation of sialuria prompts detection of liver tumor in previously reported patient.
abstract: Sialuria, a rare inborn error of metabolism, was diagnosed in a healthy 12-year-old boy through whole exome sequencing. The patient had experienced mild delays of speech and motor development, as well as persistent hepatomegaly. Identification of the 8th individual with this disorder, prompted follow-up of the mother-son pair of patients diagnosed over 15years ago. Hepatomegaly was confirmed in the now 19-year-old son, but in the 46-year-old mother a clinically silent liver tumor was detected by ultrasound and MRI. The tumor was characterized as an intrahepatic cholangiocarcinoma (IHCC) and DNA analysis of both tumor and normal liver tissue confirmed the original GNE mutation. As the maternal grandmother in the latter family died at age 49years of a liver tumor, a retrospective study of the remaining pathology slides was conducted and confirmed it to have been an IHCC as well. The overall observation generated the hypothesis that sialuria may predispose to development of this form of liver cancer. As proof of sialuria in the grandmother could not be obtained, an alternate cause of IHCC cannot be ruled out. In a series of 102 patients with IHCC, not a single instance was found with the allosteric site mutation in the GNE gene. This confirms that sialuria is rare even in a selected group of patients, but does not invalidate the concern that sialuria may be a risk factor for IHCC.
  
  
  
  Sialuria is a rare inborn error of metabolism characterized by excessive synthesis and urinary excretion of free sialic acid with only minimal clinical morbidity in early childhood, but may be a risk factor for intrahepatic cholangiocarcinoma in adulthood.
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA. Electronic address: neena@ggc.org.
authors.forename: Neena L
authors.initials: NL
authors.lastname: Champaigne
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Jules G
authors.initials: JG
authors.lastname: Leroy
authors.affiliation: Duke University Medical Center, Division of Medical Genetics, Durham, NC, USA.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.affiliation: Delta General Hospital, Department of Gastroenterology & Hepatology, Department of Pathology, Roeselare, Belgium.
authors.forename: Jochen
authors.initials: J
authors.lastname: Decaestecker
authors.affiliation: Delta General Hospital, Department of Gastroenterology & Hepatology, Department of Pathology, Roeselare, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: Steenkiste
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Alka
authors.initials: A
authors.lastname: Chaubey
authors.affiliation: Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby, British Columbia, Canada.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Li
authors.affiliation: University Hospital Leuven, Department of Hepatology, Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.affiliation: Ghent University Hospital, School of Medicine, N. Goormaghtigh Institute for Pathology, Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Van Dorpe
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Pollard
authors.affiliation: Duke University Medical Center, Division of Medical Genetics, Durham, NC, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goldstein
authors.affiliation: Ghent University Hospital, School of Medicine, N. Goormaghtigh Institute for Pathology, Ghent, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Libbrecht
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Basehore
authors.affiliation: Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby, British Columbia, Canada.
authors.forename: Nansheng
authors.initials: N
authors.lastname: Chen
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Department of Hepatobiliary Medicine, Shanghai, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Hu
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Wood
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Friez
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
mesh_terms: D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D002648:Child; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D006529:Hepatomegaly / Q000175:diagnosis; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis / Q000652:urine; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D029461:Sialic Acid Storage Disease / Q000175:diagnosis / Q000235:genetics*; D000073359:Exome Sequencing; D055815:Young Adult
chemical_list: D019158:N-Acetylneuraminic Acid
keywords: Hepatomegaly; Intrahepatic cholangiocarcinoma; Sialic acids; Sialuria; UDP acetylglucosamine-2-epimerase