PMID- 23900835
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140122
LR  - 20211021
IS  - 2192-8304 (Print)
IS  - 2192-8312 (Electronic)
IS  - 2192-8304 (Linking)
VI  - 12
DP  - 2014
TI  - Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a 
      Common Novel SLC17A5 Mutation.
PG  - 79-84
LID - 10.1007/8904_2013_247 [doi]
AB  - Infantile sialic acid storage disease (ISSD) is a lysosomal storage disease 
      characterized by accumulation of covalently unlinked (free) sialic acid in 
      multiple tissues. ISSD and Salla disease (a predominantly neurological disorder) 
      are allelic disorders caused by recessive mutations of a lysosomal anionic 
      monosaccharide transporter, SLC17A5. While Salla disease is common in Finland due 
      to a founder-effect mutation (p.Arg39Cys), ISSD is comparatively rare in all 
      populations studied.Here, we describe the clinical and molecular features of two 
      unrelated Canadian Inuit neonates with a virtually identical presentation of 
      ISSD. Both individuals presented antenatally with fetal hydrops, dying shortly 
      following delivery. Urinary free sialic acid excretion was markedly increased in 
      the one case in which urine could be obtained for testing; postmortem examination 
      showed a picture of widespread lysosomal storage in both. Both children were 
      homozygous for a novel splice site mutation (NM_012434:c.526-2A>G) resulting in 
      skipping of exon 4 and an ensuing frameshift. Analysis of a further 129 
      pan-Arctic Inuit controls demonstrated a heterozygous carrier rate of 1/129 (~0.4 
      %) in our sample. Interestingly, lysosomal enzyme studies showed an unexplained 
      ninefold increase in neuraminidase activity, with lesser elevations in the 
      activities of several other lysosomal enzymes. Our results raise the possibility 
      of a common founder mutation presenting as hydrops in this population. 
      Furthermore, if confirmed in subsequent cases, the marked induction of 
      neuraminidase activity seen here may prove useful in the clinical diagnosis of 
      ISSD.
FAU - Lines, Matthew A
AU  - Lines MA
AD  - Division of Metabolics and Newborn Screening, University of Ottawa, Children's 
      Hospital of Eastern Ontario, 401 Smyth Road, K1H 8L1, Ottawa, ON, Canada.
FAU - Rupar, C Anthony
AU  - Rupar CA
FAU - Rip, Jack W
AU  - Rip JW
FAU - Baskin, Berivan
AU  - Baskin B
FAU - Ray, Peter N
AU  - Ray PN
FAU - Hegele, Robert A
AU  - Hegele RA
FAU - Grynspan, David
AU  - Grynspan D
FAU - Michaud, Jean
AU  - Michaud J
FAU - Geraghty, Michael T
AU  - Geraghty MT
LA  - eng
PT  - Journal Article
DEP - 20130731
PL  - United States
TA  - JIMD Rep
JT  - JIMD reports
JID - 101568557
PMC - PMC3897797
EDAT- 2013/08/01 06:00
MHDA- 2013/08/01 06:01
PMCR- 2013/07/31
CRDT- 2013/08/01 06:00
PHST- 2013/04/12 00:00 [received]
PHST- 2013/06/10 00:00 [accepted]
PHST- 2013/06/05 00:00 [revised]
PHST- 2013/08/01 06:00 [entrez]
PHST- 2013/08/01 06:00 [pubmed]
PHST- 2013/08/01 06:01 [medline]
PHST- 2013/07/31 00:00 [pmc-release]
AID - 247 [pii]
AID - 10.1007/8904_2013_247 [doi]
PST - ppublish
SO  - JIMD Rep. 2014;12:79-84. doi: 10.1007/8904_2013_247. Epub 2013 Jul 31.