The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency

The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient regis...

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Detalhes bibliográficos
Autores: Juliá Palacios, Natalia, Hübschmann, Oya Kuseyri, Olivella, Mireia, Pons, Roser, Horvath, Gabriella, Lücke, Thomas, Cheuk-Wing, Fung, Wong, Suet-Na, Cortès Saladelafont, Elisenda, Rovira Remisa, Mar, Yıldız, Yilmaz, Mercimek-Andrews, Saadet, Assmann, Birgit, Stevanovic, Galina, Manti, Filippo, Brennenstuhl, Heiko, Jung-Klawitter, Sabine, Jeltsch, Kathrin, Serap Sivri, H., Garbade, Sven F., García Cazorla, Àngels, Opladen, Thomas
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:UVic-UCC
Repositorio:RiUVic. Repositori institucional de la UVic-UCC
OAI Identifier:oai:dnet:riuvic______::33a0abcfff7cf206e3b6e741b6fb703d
Acesso em linha:http://hdl.handle.net/10854/180834
https://doi.org/10.1002/jimd.12723
Access Level:acceso abierto
Palavra-chave:Fenotip
Genètica
SSADHD
575
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spelling The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiencyJuliá Palacios, NataliaHübschmann, Oya KuseyriOlivella, MireiaPons, RoserHorvath, GabriellaLücke, ThomasCheuk-Wing, FungWong, Suet-NaCortès Saladelafont, ElisendaRovira Remisa, MarYıldız, YilmazMercimek-Andrews, SaadetAssmann, BirgitStevanovic, GalinaManti, FilippoBrennenstuhl, HeikoJung-Klawitter, SabineJeltsch, KathrinSerap Sivri, H.Garbade, Sven F.García Cazorla, ÀngelsOpladen, ThomasFenotipGenèticaSSADHD575The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient registry of the International Working Group on Neurotransmitter related Disorders (iNTD) were studied with in silico analyses, pathogenicity scores and molecular modeling of ALDH5A1 variants. Leading initial symptoms, with onset in infancy, were developmental delay and hypotonia. Year of birth and specific initial symptoms influenced the diagnostic delay. Clinical phenotype of 26 individuals (median 12 years, range 1.8–33.4 years) showed a diversifying course in follow-up: 77% behavioral problems, 76% coordination problems, 73% speech disorders, 58% epileptic seizures and 40% movement disorders. After ataxia, dystonia (19%), chorea (11%) and hypokinesia (15%) were the most frequent movement disorders. Involvement of the dentate nucleus in brain imaging was observed together with movement disorders or coordination problems. Short attention span (78.6%) and distractibility (71.4%) were the most frequently behavior traits mentioned by parents while impulsiveness, problems communicating wishes or needs and compulsive behavior were addressed as strongly interfering with family life. Treatment was mainly aimed to control epileptic seizures and psychiatric symptoms. Four new pathogenic variants were identified. In silico scoring system, protein activity and pathogenicity score revealed a high correlation. A genotype/phenotype correlation was not observed, even in siblings. This study presents the diversifying characteristics of disease phenotype during the disease course, highlighting movement disorders, widens the knowledge on the genotypic spectrum of SSADHD and emphasizes a reliable application of in silico approaches.info:eu-repo/semantics/publishedVersionWileyUniversitat de Vic - Universitat Central de Catalunya. Grup de Recerca en Bioinformàtica i Estadística Mèdica (BEM)2026202620242024info:eu-repo/semantics/article16 p.application/pdfhttp://hdl.handle.net/10854/180834https://doi.org/10.1002/jimd.12723reponame:RiUVic. Repositori institucional de la UVic-UCCinstname:UVic-UCCInglésJournal of inherited metabolic disease, 47(3), 447-462Attribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:dnet:riuvic______::33a0abcfff7cf206e3b6e741b6fb703d2026-06-07T19:15:21Z
dc.title.none.fl_str_mv The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
title The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
spellingShingle The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
Juliá Palacios, Natalia
Fenotip
Genètica
SSADHD
575
title_short The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
title_full The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
title_fullStr The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
title_full_unstemmed The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
title_sort The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
dc.creator.none.fl_str_mv Juliá Palacios, Natalia
Hübschmann, Oya Kuseyri
Olivella, Mireia
Pons, Roser
Horvath, Gabriella
Lücke, Thomas
Cheuk-Wing, Fung
Wong, Suet-Na
Cortès Saladelafont, Elisenda
Rovira Remisa, Mar
Yıldız, Yilmaz
Mercimek-Andrews, Saadet
Assmann, Birgit
Stevanovic, Galina
Manti, Filippo
Brennenstuhl, Heiko
Jung-Klawitter, Sabine
Jeltsch, Kathrin
Serap Sivri, H.
Garbade, Sven F.
García Cazorla, Àngels
Opladen, Thomas
author Juliá Palacios, Natalia
author_facet Juliá Palacios, Natalia
Hübschmann, Oya Kuseyri
Olivella, Mireia
Pons, Roser
Horvath, Gabriella
Lücke, Thomas
Cheuk-Wing, Fung
Wong, Suet-Na
Cortès Saladelafont, Elisenda
Rovira Remisa, Mar
Yıldız, Yilmaz
Mercimek-Andrews, Saadet
Assmann, Birgit
Stevanovic, Galina
Manti, Filippo
Brennenstuhl, Heiko
Jung-Klawitter, Sabine
Jeltsch, Kathrin
Serap Sivri, H.
Garbade, Sven F.
García Cazorla, Àngels
Opladen, Thomas
author_role author
author2 Hübschmann, Oya Kuseyri
Olivella, Mireia
Pons, Roser
Horvath, Gabriella
Lücke, Thomas
Cheuk-Wing, Fung
Wong, Suet-Na
Cortès Saladelafont, Elisenda
Rovira Remisa, Mar
Yıldız, Yilmaz
Mercimek-Andrews, Saadet
Assmann, Birgit
Stevanovic, Galina
Manti, Filippo
Brennenstuhl, Heiko
Jung-Klawitter, Sabine
Jeltsch, Kathrin
Serap Sivri, H.
Garbade, Sven F.
García Cazorla, Àngels
Opladen, Thomas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat de Vic - Universitat Central de Catalunya. Grup de Recerca en Bioinformàtica i Estadística Mèdica (BEM)
dc.subject.none.fl_str_mv Fenotip
Genètica
SSADHD
575
topic Fenotip
Genètica
SSADHD
575
description The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient registry of the International Working Group on Neurotransmitter related Disorders (iNTD) were studied with in silico analyses, pathogenicity scores and molecular modeling of ALDH5A1 variants. Leading initial symptoms, with onset in infancy, were developmental delay and hypotonia. Year of birth and specific initial symptoms influenced the diagnostic delay. Clinical phenotype of 26 individuals (median 12 years, range 1.8–33.4 years) showed a diversifying course in follow-up: 77% behavioral problems, 76% coordination problems, 73% speech disorders, 58% epileptic seizures and 40% movement disorders. After ataxia, dystonia (19%), chorea (11%) and hypokinesia (15%) were the most frequent movement disorders. Involvement of the dentate nucleus in brain imaging was observed together with movement disorders or coordination problems. Short attention span (78.6%) and distractibility (71.4%) were the most frequently behavior traits mentioned by parents while impulsiveness, problems communicating wishes or needs and compulsive behavior were addressed as strongly interfering with family life. Treatment was mainly aimed to control epileptic seizures and psychiatric symptoms. Four new pathogenic variants were identified. In silico scoring system, protein activity and pathogenicity score revealed a high correlation. A genotype/phenotype correlation was not observed, even in siblings. This study presents the diversifying characteristics of disease phenotype during the disease course, highlighting movement disorders, widens the knowledge on the genotypic spectrum of SSADHD and emphasizes a reliable application of in silico approaches.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10854/180834
https://doi.org/10.1002/jimd.12723
url http://hdl.handle.net/10854/180834
https://doi.org/10.1002/jimd.12723
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of inherited metabolic disease, 47(3), 447-462
dc.rights.none.fl_str_mv Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:RiUVic. Repositori institucional de la UVic-UCC
instname:UVic-UCC
instname_str UVic-UCC
reponame_str RiUVic. Repositori institucional de la UVic-UCC
collection RiUVic. Repositori institucional de la UVic-UCC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414835773505536
score 15,812429

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