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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/106543
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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 Técnicas2025-09-29T09:49:22Zoai: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:34982025-09-29 09:49:22.291CONICET 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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1844613528544083968 |
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13.070432 |