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

Abstract Background 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. Resu...
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Autor*in:	Silene M. Silvera-Ruiz [verfasserIn] José A. Arranz [verfasserIn] Johannes Häberle [verfasserIn] Celia J. Angaroni [verfasserIn] Miriam Bezard [verfasserIn] Norberto Guelbert [verfasserIn] Adriana Becerra [verfasserIn] Fernanda Peralta [verfasserIn] Raquel Dodelson de Kremer [verfasserIn] Laura E. Laróvere [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency

Übergeordnetes Werk:	In: Orphanet Journal of Rare Diseases - BMC, 2006, 14(2019), 1, Seite 8
Übergeordnetes Werk:	volume:14 ; year:2019 ; number:1 ; pages:8

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13023-019-1177-3

Katalog-ID:	DOAJ048251453

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520			\|a Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment.
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allfields	10.1186/s13023-019-1177-3 doi (DE-627)DOAJ048251453 (DE-599)DOAJ17dc06246177496fb683b009d2c14c63 DE-627 ger DE-627 rakwb eng Silene M. Silvera-Ruiz verfasserin aut Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment. Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R José A. Arranz verfasserin aut Johannes Häberle verfasserin aut Celia J. Angaroni verfasserin aut Miriam Bezard verfasserin aut Norberto Guelbert verfasserin aut Adriana Becerra verfasserin aut Fernanda Peralta verfasserin aut Raquel Dodelson de Kremer verfasserin aut Laura E. Laróvere verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 14(2019), 1, Seite 8 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:14 year:2019 number:1 pages:8 https://doi.org/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/article/17dc06246177496fb683b009d2c14c63 kostenfrei http://link.springer.com/article/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 8
spelling	10.1186/s13023-019-1177-3 doi (DE-627)DOAJ048251453 (DE-599)DOAJ17dc06246177496fb683b009d2c14c63 DE-627 ger DE-627 rakwb eng Silene M. Silvera-Ruiz verfasserin aut Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment. Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R José A. Arranz verfasserin aut Johannes Häberle verfasserin aut Celia J. Angaroni verfasserin aut Miriam Bezard verfasserin aut Norberto Guelbert verfasserin aut Adriana Becerra verfasserin aut Fernanda Peralta verfasserin aut Raquel Dodelson de Kremer verfasserin aut Laura E. Laróvere verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 14(2019), 1, Seite 8 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:14 year:2019 number:1 pages:8 https://doi.org/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/article/17dc06246177496fb683b009d2c14c63 kostenfrei http://link.springer.com/article/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 8
allfields_unstemmed	10.1186/s13023-019-1177-3 doi (DE-627)DOAJ048251453 (DE-599)DOAJ17dc06246177496fb683b009d2c14c63 DE-627 ger DE-627 rakwb eng Silene M. Silvera-Ruiz verfasserin aut Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment. Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R José A. Arranz verfasserin aut Johannes Häberle verfasserin aut Celia J. Angaroni verfasserin aut Miriam Bezard verfasserin aut Norberto Guelbert verfasserin aut Adriana Becerra verfasserin aut Fernanda Peralta verfasserin aut Raquel Dodelson de Kremer verfasserin aut Laura E. Laróvere verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 14(2019), 1, Seite 8 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:14 year:2019 number:1 pages:8 https://doi.org/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/article/17dc06246177496fb683b009d2c14c63 kostenfrei http://link.springer.com/article/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 8
allfieldsGer	10.1186/s13023-019-1177-3 doi (DE-627)DOAJ048251453 (DE-599)DOAJ17dc06246177496fb683b009d2c14c63 DE-627 ger DE-627 rakwb eng Silene M. Silvera-Ruiz verfasserin aut Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment. Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R José A. Arranz verfasserin aut Johannes Häberle verfasserin aut Celia J. Angaroni verfasserin aut Miriam Bezard verfasserin aut Norberto Guelbert verfasserin aut Adriana Becerra verfasserin aut Fernanda Peralta verfasserin aut Raquel Dodelson de Kremer verfasserin aut Laura E. Laróvere verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 14(2019), 1, Seite 8 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:14 year:2019 number:1 pages:8 https://doi.org/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/article/17dc06246177496fb683b009d2c14c63 kostenfrei http://link.springer.com/article/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 8
allfieldsSound	10.1186/s13023-019-1177-3 doi (DE-627)DOAJ048251453 (DE-599)DOAJ17dc06246177496fb683b009d2c14c63 DE-627 ger DE-627 rakwb eng Silene M. Silvera-Ruiz verfasserin aut Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment. Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R José A. Arranz verfasserin aut Johannes Häberle verfasserin aut Celia J. Angaroni verfasserin aut Miriam Bezard verfasserin aut Norberto Guelbert verfasserin aut Adriana Becerra verfasserin aut Fernanda Peralta verfasserin aut Raquel Dodelson de Kremer verfasserin aut Laura E. Laróvere verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 14(2019), 1, Seite 8 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:14 year:2019 number:1 pages:8 https://doi.org/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/article/17dc06246177496fb683b009d2c14c63 kostenfrei http://link.springer.com/article/10.1186/s13023-019-1177-3 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 8
language	English
source	In Orphanet Journal of Rare Diseases 14(2019), 1, Seite 8 volume:14 year:2019 number:1 pages:8
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topic_facet	Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency Medicine R
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container_title	Orphanet Journal of Rare Diseases
authorswithroles_txt_mv	Silene M. Silvera-Ruiz @@aut@@ José A. Arranz @@aut@@ Johannes Häberle @@aut@@ Celia J. Angaroni @@aut@@ Miriam Bezard @@aut@@ Norberto Guelbert @@aut@@ Adriana Becerra @@aut@@ Fernanda Peralta @@aut@@ Raquel Dodelson de Kremer @@aut@@ Laura E. Laróvere @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
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author	Silene M. Silvera-Ruiz
spellingShingle	Silene M. Silvera-Ruiz misc Urea cycle defects misc Hyperammonemia misc Ornithine transcarbamylase deficiency misc Argininosuccinate synthetase deficiency misc Argininosuccinate lyase deficiency misc Medicine misc R Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
authorStr	Silene M. Silvera-Ruiz
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topic_title	Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings Urea cycle defects Hyperammonemia Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency Argininosuccinate lyase deficiency
topic	misc Urea cycle defects misc Hyperammonemia misc Ornithine transcarbamylase deficiency misc Argininosuccinate synthetase deficiency misc Argininosuccinate lyase deficiency misc Medicine misc R
topic_unstemmed	misc Urea cycle defects misc Hyperammonemia misc Ornithine transcarbamylase deficiency misc Argininosuccinate synthetase deficiency misc Argininosuccinate lyase deficiency misc Medicine misc R
topic_browse	misc Urea cycle defects misc Hyperammonemia misc Ornithine transcarbamylase deficiency misc Argininosuccinate synthetase deficiency misc Argininosuccinate lyase deficiency misc Medicine misc R
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title	Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
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title_full	Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
author_sort	Silene M. Silvera-Ruiz
journal	Orphanet Journal of Rare Diseases
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author_browse	Silene M. Silvera-Ruiz José A. Arranz Johannes Häberle Celia J. Angaroni Miriam Bezard Norberto Guelbert Adriana Becerra Fernanda Peralta Raquel Dodelson de Kremer Laura E. Laróvere
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author-letter	Silene M. Silvera-Ruiz
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title_sort	urea cycle disorders in argentine patients: clinical presentation, biochemical and genetic findings
title_auth	Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
abstract	Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment.
abstractGer	Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment.
abstract_unstemmed	Abstract Background 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. Results 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. Conclusions 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, early diagnosis, and timely treatment.
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title_short	Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
url	https://doi.org/10.1186/s13023-019-1177-3 https://doaj.org/article/17dc06246177496fb683b009d2c14c63 http://link.springer.com/article/10.1186/s13023-019-1177-3 https://doaj.org/toc/1750-1172
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