Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings

Autores
Silvera Ruiz, Silene Maite; Arranz, José A.; Häberle, Johannes; Angaroni, Celia Juana; Bezard, Miriam; Guelbert, Norberto Bernardo; Becerra, Adriana Berónica; Peralta, Maria Fernanda; Dodelson de Kremer, Raquel; Laróvere, Laura Elena
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina. Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 cases), and a 28% (6/21) disability rate among the survivors. Most patients in our case series showed severe neonatal onset, with high morbidity/ mortality. We detected in total 19 mutations, most of them recurrent and of high frequency worldwide. Noteworthy, we highlight the presence of a geographic cluster with high prevalence of a point mutation in the ASS1 gene. This study suggests that these disorders may be more frequent than commonly assumed, and stresses the need for increased awareness amongst health professionals and greater availability of diagnostic tools for accurate identification, earlydiagnosis, and timely treatment.
Fil: Silvera Ruiz, Silene Maite. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Arranz, José A.. Laboratori de Metabolopaties, Hospital Vall Dhebron; España
Fil: Häberle, Johannes. University Children's Hospital And Children´s Research; Suiza
Fil: Angaroni, Celia Juana. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Bezard, Miriam. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Peralta, Maria Fernanda. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Laróvere, Laura Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Materia
UREA CYCLE DEFECTS
HYPERAMMONEMIA
ARGENTINE PATIENTS
INHERITED METABOLIC DISORDERS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/106543
Acceder
id CONICETDig_82ae13fe3a72e0f9058522db9f1a022d
oai_identifier_str oai:ri.conicet.gov.ar:11336/106543
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findingsSilvera Ruiz, Silene MaiteArranz, José A.Häberle, JohannesAngaroni, Celia JuanaBezard, MiriamGuelbert, Norberto BernardoBecerra, Adriana BerónicaPeralta, Maria FernandaDodelson de Kremer, RaquelLaróvere, Laura ElenaUREA CYCLE DEFECTSHYPERAMMONEMIAARGENTINE PATIENTSINHERITED METABOLIC DISORDERShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina. Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 cases), and a 28% (6/21) disability rate among the survivors. Most patients in our case series showed severe neonatal onset, with high morbidity/ mortality. We detected in total 19 mutations, most of them recurrent and of high frequency worldwide. Noteworthy, we highlight the presence of a geographic cluster with high prevalence of a point mutation in the ASS1 gene. This study suggests that these disorders may be more frequent than commonly assumed, and stresses the need for increased awareness amongst health professionals and greater availability of diagnostic tools for accurate identification, earlydiagnosis, and timely treatment.Fil: Silvera Ruiz, Silene Maite. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Arranz, José A.. Laboratori de Metabolopaties, Hospital Vall Dhebron; EspañaFil: Häberle, Johannes. University Children's Hospital And Children´s Research; SuizaFil: Angaroni, Celia Juana. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Bezard, Miriam. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; ArgentinaFil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; ArgentinaFil: Peralta, Maria Fernanda. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Laróvere, Laura Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaBioMed Central2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/106543Silvera Ruiz, Silene Maite; Arranz, José A.; Häberle, Johannes; Angaroni, Celia Juana; Bezard, Miriam; et al.; Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings; BioMed Central; Orphanet Journal Of Rare Diseases; 14; 1; 8-20191750-1172CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1177-3info:eu-repo/semantics/altIdentifier/doi/10.1186/s13023-019-1177-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:18:47Zoai:ri.conicet.gov.ar:11336/106543instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:18:48.23CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
title Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
spellingShingle Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
Silvera Ruiz, Silene Maite
UREA CYCLE DEFECTS
HYPERAMMONEMIA
ARGENTINE PATIENTS
INHERITED METABOLIC DISORDERS
title_short Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
title_full Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
title_fullStr Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
title_full_unstemmed Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
title_sort Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings
dc.creator.none.fl_str_mv Silvera Ruiz, Silene Maite
Arranz, José A.
Häberle, Johannes
Angaroni, Celia Juana
Bezard, Miriam
Guelbert, Norberto Bernardo
Becerra, Adriana Berónica
Peralta, Maria Fernanda
Dodelson de Kremer, Raquel
Laróvere, Laura Elena
author Silvera Ruiz, Silene Maite
author_facet Silvera Ruiz, Silene Maite
Arranz, José A.
Häberle, Johannes
Angaroni, Celia Juana
Bezard, Miriam
Guelbert, Norberto Bernardo
Becerra, Adriana Berónica
Peralta, Maria Fernanda
Dodelson de Kremer, Raquel
Laróvere, Laura Elena
author_role author
author2 Arranz, José A.
Häberle, Johannes
Angaroni, Celia Juana
Bezard, Miriam
Guelbert, Norberto Bernardo
Becerra, Adriana Berónica
Peralta, Maria Fernanda
Dodelson de Kremer, Raquel
Laróvere, Laura Elena
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv UREA CYCLE DEFECTS
HYPERAMMONEMIA
ARGENTINE PATIENTS
INHERITED METABOLIC DISORDERS
topic UREA CYCLE DEFECTS
HYPERAMMONEMIA
ARGENTINE PATIENTS
INHERITED METABOLIC DISORDERS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina. Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 cases), and a 28% (6/21) disability rate among the survivors. Most patients in our case series showed severe neonatal onset, with high morbidity/ mortality. We detected in total 19 mutations, most of them recurrent and of high frequency worldwide. Noteworthy, we highlight the presence of a geographic cluster with high prevalence of a point mutation in the ASS1 gene. This study suggests that these disorders may be more frequent than commonly assumed, and stresses the need for increased awareness amongst health professionals and greater availability of diagnostic tools for accurate identification, earlydiagnosis, and timely treatment.
Fil: Silvera Ruiz, Silene Maite. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Arranz, José A.. Laboratori de Metabolopaties, Hospital Vall Dhebron; España
Fil: Häberle, Johannes. University Children's Hospital And Children´s Research; Suiza
Fil: Angaroni, Celia Juana. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Bezard, Miriam. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Peralta, Maria Fernanda. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Laróvere, Laura Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
description The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina. Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 cases), and a 28% (6/21) disability rate among the survivors. Most patients in our case series showed severe neonatal onset, with high morbidity/ mortality. We detected in total 19 mutations, most of them recurrent and of high frequency worldwide. Noteworthy, we highlight the presence of a geographic cluster with high prevalence of a point mutation in the ASS1 gene. This study suggests that these disorders may be more frequent than commonly assumed, and stresses the need for increased awareness amongst health professionals and greater availability of diagnostic tools for accurate identification, earlydiagnosis, and timely treatment.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/106543
Silvera Ruiz, Silene Maite; Arranz, José A.; Häberle, Johannes; Angaroni, Celia Juana; Bezard, Miriam; et al.; Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings; BioMed Central; Orphanet Journal Of Rare Diseases; 14; 1; 8-2019
1750-1172
CONICET Digital
CONICET
url http://hdl.handle.net/11336/106543
identifier_str_mv Silvera Ruiz, Silene Maite; Arranz, José A.; Häberle, Johannes; Angaroni, Celia Juana; Bezard, Miriam; et al.; Urea cycle disorders in Argentine patients: Clinical presentation, biochemical and genetic findings; BioMed Central; Orphanet Journal Of Rare Diseases; 14; 1; 8-2019
1750-1172
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1177-3
info:eu-repo/semantics/altIdentifier/doi/10.1186/s13023-019-1177-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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