Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Sunita Bijarnia-Mahay [verfasserIn] Johannes Häberle [verfasserIn] Anil B. Jalan [verfasserIn] Ratna Dua Puri [verfasserIn] Sudha Kohli [verfasserIn] Ketki Kudalkar [verfasserIn] Véronique Rüfenacht [verfasserIn] Deepti Gupta [verfasserIn] Deepshikha Maurya [verfasserIn] Jyotsna Verma [verfasserIn] Yosuke Shigematsu [verfasserIn] Seiji Yamaguchi [verfasserIn] Renu Saxena [verfasserIn] Ishwar C. Verma [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation

Übergeordnetes Werk:	In: Orphanet Journal of Rare Diseases - BMC, 2006, 13(2018), 1, Seite 12
Übergeordnetes Werk:	volume:13 ; year:2018 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13023-018-0908-1

Katalog-ID:	DOAJ014251965

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245	1	0	\|a Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
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520			\|a Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
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allfields	10.1186/s13023-018-0908-1 doi (DE-627)DOAJ014251965 (DE-599)DOAJ65d79e3249d4413dae7e12748ea823af DE-627 ger DE-627 rakwb eng Sunita Bijarnia-Mahay verfasserin aut Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R Johannes Häberle verfasserin aut Anil B. Jalan verfasserin aut Ratna Dua Puri verfasserin aut Sudha Kohli verfasserin aut Ketki Kudalkar verfasserin aut Véronique Rüfenacht verfasserin aut Deepti Gupta verfasserin aut Deepshikha Maurya verfasserin aut Jyotsna Verma verfasserin aut Yosuke Shigematsu verfasserin aut Seiji Yamaguchi verfasserin aut Renu Saxena verfasserin aut Ishwar C. Verma verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 12 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/article/65d79e3249d4413dae7e12748ea823af kostenfrei http://link.springer.com/article/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 13 2018 1 12
spelling	10.1186/s13023-018-0908-1 doi (DE-627)DOAJ014251965 (DE-599)DOAJ65d79e3249d4413dae7e12748ea823af DE-627 ger DE-627 rakwb eng Sunita Bijarnia-Mahay verfasserin aut Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R Johannes Häberle verfasserin aut Anil B. Jalan verfasserin aut Ratna Dua Puri verfasserin aut Sudha Kohli verfasserin aut Ketki Kudalkar verfasserin aut Véronique Rüfenacht verfasserin aut Deepti Gupta verfasserin aut Deepshikha Maurya verfasserin aut Jyotsna Verma verfasserin aut Yosuke Shigematsu verfasserin aut Seiji Yamaguchi verfasserin aut Renu Saxena verfasserin aut Ishwar C. Verma verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 12 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/article/65d79e3249d4413dae7e12748ea823af kostenfrei http://link.springer.com/article/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 13 2018 1 12
allfields_unstemmed	10.1186/s13023-018-0908-1 doi (DE-627)DOAJ014251965 (DE-599)DOAJ65d79e3249d4413dae7e12748ea823af DE-627 ger DE-627 rakwb eng Sunita Bijarnia-Mahay verfasserin aut Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R Johannes Häberle verfasserin aut Anil B. Jalan verfasserin aut Ratna Dua Puri verfasserin aut Sudha Kohli verfasserin aut Ketki Kudalkar verfasserin aut Véronique Rüfenacht verfasserin aut Deepti Gupta verfasserin aut Deepshikha Maurya verfasserin aut Jyotsna Verma verfasserin aut Yosuke Shigematsu verfasserin aut Seiji Yamaguchi verfasserin aut Renu Saxena verfasserin aut Ishwar C. Verma verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 12 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/article/65d79e3249d4413dae7e12748ea823af kostenfrei http://link.springer.com/article/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 13 2018 1 12
allfieldsGer	10.1186/s13023-018-0908-1 doi (DE-627)DOAJ014251965 (DE-599)DOAJ65d79e3249d4413dae7e12748ea823af DE-627 ger DE-627 rakwb eng Sunita Bijarnia-Mahay verfasserin aut Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R Johannes Häberle verfasserin aut Anil B. Jalan verfasserin aut Ratna Dua Puri verfasserin aut Sudha Kohli verfasserin aut Ketki Kudalkar verfasserin aut Véronique Rüfenacht verfasserin aut Deepti Gupta verfasserin aut Deepshikha Maurya verfasserin aut Jyotsna Verma verfasserin aut Yosuke Shigematsu verfasserin aut Seiji Yamaguchi verfasserin aut Renu Saxena verfasserin aut Ishwar C. Verma verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 12 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/article/65d79e3249d4413dae7e12748ea823af kostenfrei http://link.springer.com/article/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 13 2018 1 12
allfieldsSound	10.1186/s13023-018-0908-1 doi (DE-627)DOAJ014251965 (DE-599)DOAJ65d79e3249d4413dae7e12748ea823af DE-627 ger DE-627 rakwb eng Sunita Bijarnia-Mahay verfasserin aut Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R Johannes Häberle verfasserin aut Anil B. Jalan verfasserin aut Ratna Dua Puri verfasserin aut Sudha Kohli verfasserin aut Ketki Kudalkar verfasserin aut Véronique Rüfenacht verfasserin aut Deepti Gupta verfasserin aut Deepshikha Maurya verfasserin aut Jyotsna Verma verfasserin aut Yosuke Shigematsu verfasserin aut Seiji Yamaguchi verfasserin aut Renu Saxena verfasserin aut Ishwar C. Verma verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 12 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/article/65d79e3249d4413dae7e12748ea823af kostenfrei http://link.springer.com/article/10.1186/s13023-018-0908-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 13 2018 1 12
language	English
source	In Orphanet Journal of Rare Diseases 13(2018), 1, Seite 12 volume:13 year:2018 number:1 pages:12
sourceStr	In Orphanet Journal of Rare Diseases 13(2018), 1, Seite 12 volume:13 year:2018 number:1 pages:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation Medicine R
isfreeaccess_bool	true
container_title	Orphanet Journal of Rare Diseases
authorswithroles_txt_mv	Sunita Bijarnia-Mahay @@aut@@ Johannes Häberle @@aut@@ Anil B. Jalan @@aut@@ Ratna Dua Puri @@aut@@ Sudha Kohli @@aut@@ Ketki Kudalkar @@aut@@ Véronique Rüfenacht @@aut@@ Deepti Gupta @@aut@@ Deepshikha Maurya @@aut@@ Jyotsna Verma @@aut@@ Yosuke Shigematsu @@aut@@ Seiji Yamaguchi @@aut@@ Renu Saxena @@aut@@ Ishwar C. Verma @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	50900637X
id	DOAJ014251965
language_de	englisch
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These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. 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author	Sunita Bijarnia-Mahay
spellingShingle	Sunita Bijarnia-Mahay misc Urea cycle misc UCD misc OTC deficiency misc Citrullinemia misc Argininosuccinic aciduria misc Mutation misc Medicine misc R Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
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topic_title	Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing Urea cycle UCD OTC deficiency Citrullinemia Argininosuccinic aciduria Mutation
topic	misc Urea cycle misc UCD misc OTC deficiency misc Citrullinemia misc Argininosuccinic aciduria misc Mutation misc Medicine misc R
topic_unstemmed	misc Urea cycle misc UCD misc OTC deficiency misc Citrullinemia misc Argininosuccinic aciduria misc Mutation misc Medicine misc R
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title	Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
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title_full	Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
author_sort	Sunita Bijarnia-Mahay
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author_browse	Sunita Bijarnia-Mahay Johannes Häberle Anil B. Jalan Ratna Dua Puri Sudha Kohli Ketki Kudalkar Véronique Rüfenacht Deepti Gupta Deepshikha Maurya Jyotsna Verma Yosuke Shigematsu Seiji Yamaguchi Renu Saxena Ishwar C. Verma
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title_sort	urea cycle disorders in india: clinical course, biochemical and genetic investigations, and prenatal testing
title_auth	Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
abstract	Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
abstractGer	Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
abstract_unstemmed	Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G < A (p.Arg157His) and c.1168G < A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
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title_short	Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
url	https://doi.org/10.1186/s13023-018-0908-1 https://doaj.org/article/65d79e3249d4413dae7e12748ea823af http://link.springer.com/article/10.1186/s13023-018-0908-1 https://doaj.org/toc/1750-1172
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In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. 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Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

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