Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation
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 a...
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ftunivwestonta:oai:ir.lib.uwo.ca:paedpub-3087 2023-10-01T03:54:12+02:00 Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation Lines, Matthew A. Rupar, C. Anthony Rip, Jack W. Baskin, Berivan Ray, Peter N. Hegele, Robert A. Grynspan, David Michaud, Jean Geraghty, Michael T. 2014-01-01T08:00:00Z text/html https://ir.lib.uwo.ca/paedpub/2079 https://doi.org/10.1007/8904_2013_247 https://ir.lib.uwo.ca/context/paedpub/article/3087/type/native/viewcontent/978_3_319_03461_4.pdf unknown Scholarship@Western https://ir.lib.uwo.ca/paedpub/2079 doi:10.1007/8904_2013_247 https://ir.lib.uwo.ca/context/paedpub/article/3087/type/native/viewcontent/978_3_319_03461_4.pdf Paediatrics Publications Fetal hydrops Lysosomal storage disease Neuraminidase activity Sialic acid SLC17A5 Mutation article 2014 ftunivwestonta https://doi.org/10.1007/8904_2013_247 2023-09-03T07:43:15Z 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. Article in Journal/Newspaper Arctic inuit The University of Western Ontario: Scholarship@Western Arctic Salla ENVELOPE(28.667,28.667,66.833,66.833) 79 84 |
institution |
Open Polar |
collection |
The University of Western Ontario: Scholarship@Western |
op_collection_id |
ftunivwestonta |
language |
unknown |
topic |
Fetal hydrops Lysosomal storage disease Neuraminidase activity Sialic acid SLC17A5 Mutation |
spellingShingle |
Fetal hydrops Lysosomal storage disease Neuraminidase activity Sialic acid SLC17A5 Mutation Lines, Matthew A. Rupar, C. Anthony Rip, Jack W. Baskin, Berivan Ray, Peter N. Hegele, Robert A. Grynspan, David Michaud, Jean Geraghty, Michael T. Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
topic_facet |
Fetal hydrops Lysosomal storage disease Neuraminidase activity Sialic acid SLC17A5 Mutation |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Lines, Matthew A. Rupar, C. Anthony Rip, Jack W. Baskin, Berivan Ray, Peter N. Hegele, Robert A. Grynspan, David Michaud, Jean Geraghty, Michael T. |
author_facet |
Lines, Matthew A. Rupar, C. Anthony Rip, Jack W. Baskin, Berivan Ray, Peter N. Hegele, Robert A. Grynspan, David Michaud, Jean Geraghty, Michael T. |
author_sort |
Lines, Matthew A. |
title |
Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
title_short |
Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
title_full |
Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
title_fullStr |
Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
title_full_unstemmed |
Infantile sialic acid storage disease: Two unrelated inuit cases homozygous for a common novel SLC17A5 mutation |
title_sort |
infantile sialic acid storage disease: two unrelated inuit cases homozygous for a common novel slc17a5 mutation |
publisher |
Scholarship@Western |
publishDate |
2014 |
url |
https://ir.lib.uwo.ca/paedpub/2079 https://doi.org/10.1007/8904_2013_247 https://ir.lib.uwo.ca/context/paedpub/article/3087/type/native/viewcontent/978_3_319_03461_4.pdf |
long_lat |
ENVELOPE(28.667,28.667,66.833,66.833) |
geographic |
Arctic Salla |
geographic_facet |
Arctic Salla |
genre |
Arctic inuit |
genre_facet |
Arctic inuit |
op_source |
Paediatrics Publications |
op_relation |
https://ir.lib.uwo.ca/paedpub/2079 doi:10.1007/8904_2013_247 https://ir.lib.uwo.ca/context/paedpub/article/3087/type/native/viewcontent/978_3_319_03461_4.pdf |
op_doi |
https://doi.org/10.1007/8904_2013_247 |
container_start_page |
79 |
op_container_end_page |
84 |
_version_ |
1778521608694005760 |