Sialuria: Ninth Patient Described Has a Novel Mutation in GNE
Sialuria is a rare autosomal dominant inborn error of metabolism characterized by cytoplasmic accumulation and urinary excretion of gram quantities of free sialic acid due to failure of feedback inhibition of the rate-limiting enzyme in the sialic acid synthesis pathway, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). To date, eight cases had been published worldwide, all with heterozygous missense variants at the allosteric site, specifically at Arginine 294 (formerly 263) and Arginine 297 (formerly 266) of GNE. The described cases so far have rather homogeneous clinical features which include developmental delay, mildly coarse features, hepatomegaly and prolonged neonatal jaundice. The apparent rarity of this disorder is hypothesized to be due to the variable and sometimes transient nature of the clinical features and to the absence of routine testing for urinary sialic acids. Here we present the ninth case of sialuria diagnosed in a child investigated because of clinical signs and symptoms and furthermore describe a novel pathogenic variant in the associated gene, GNE.
KeywordsGNE Hepatomegaly Sialic acids Sialuria UDP acetylglucosamine-2-epimerase
The authors would like to thank Dr. Marjan Huizing, Professor William Gahl and Professor Edwin Kirk for helpful discussion, Dr. Tim Wood for the cell fractionation and Samuel Wang, who did an initial literature search.
- Adams D, Gahl WA (2003) Free sialic acid storage disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, LJH B, Stephens K, Amemiya A (eds) Source GeneReviews® [internet]. University of Washington, SeattleGoogle Scholar
- Varki A, Schauer R (2009) Sialic acids. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of gylcobiology, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
- Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G (2010) Protein structure analysis of mutations causing inheritable diseases. An e-science approach with life scientist friendly interfaces. BMC Bioinf 11(1):548. http://www.cmbi.ru.nl/hope/report/5ac20123e5058a00891ff6d6/ CrossRefGoogle Scholar