Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients

Autores
Laróvere, Laura Elena; Fairbanks, Lynette D.; Jinnah, H. A.; Guelbert, Norberto Bernardo; Escuredo, Emilia; Becerra, Adriana Berónica; Dodelson de Kremer, Raquel
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.
Fil: Laróvere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fairbanks, Lynette D.. Purine Research Laboratory, St. Thomass Hosp; Reino Unido
Fil: Jinnah, H. A.. University of Emory; Estados Unidos
Fil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Escuredo, Emilia. Purine Research Laboratory, St. Thomass Hosp; Reino Unido
Fil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Materia
Hypoxanthine-guanine phosphoribosyltransferase deficiency
Hyperuricemia
Lesch-Nyhan disease
Lesch-Nyhan variant
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:11336/150718
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/150718
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patientsLaróvere, Laura ElenaFairbanks, Lynette D.Jinnah, H. A.Guelbert, Norberto BernardoEscuredo, EmiliaBecerra, Adriana BerónicaDodelson de Kremer, RaquelHypoxanthine-guanine phosphoribosyltransferase deficiencyHyperuricemiaLesch-Nyhan diseaseLesch-Nyhan varianthttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.Fil: Laróvere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fairbanks, Lynette D.. Purine Research Laboratory, St. Thomass Hosp; Reino UnidoFil: Jinnah, H. A.. University of Emory; Estados UnidosFil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; ArgentinaFil: Escuredo, Emilia. Purine Research Laboratory, St. Thomass Hosp; Reino UnidoFil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; ArgentinaFil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaScielo2021-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/150718Laróvere, Laura Elena; Fairbanks, Lynette D.; Jinnah, H. A.; Guelbert, Norberto Bernardo; Escuredo, Emilia; et al.; Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients; Scielo; Journal of Inborn Errors of Metabolism and Screening; 3-20212326-4594CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1590/2326-4594-jiems-2020-0027info:eu-repo/semantics/altIdentifier/url/https://www.scielo.br/j/jiems/a/bJKcpfbPCzLKSNMCqcHBGqD/?lang=eninfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:40:03Zoai:ri.conicet.gov.ar:11336/150718instacron: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 10:40:03.994CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
title Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
spellingShingle Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
Laróvere, Laura Elena
Hypoxanthine-guanine phosphoribosyltransferase deficiency
Hyperuricemia
Lesch-Nyhan disease
Lesch-Nyhan variant
title_short Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
title_full Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
title_fullStr Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
title_full_unstemmed Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
title_sort Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients
dc.creator.none.fl_str_mv Laróvere, Laura Elena
Fairbanks, Lynette D.
Jinnah, H. A.
Guelbert, Norberto Bernardo
Escuredo, Emilia
Becerra, Adriana Berónica
Dodelson de Kremer, Raquel
author Laróvere, Laura Elena
author_facet Laróvere, Laura Elena
Fairbanks, Lynette D.
Jinnah, H. A.
Guelbert, Norberto Bernardo
Escuredo, Emilia
Becerra, Adriana Berónica
Dodelson de Kremer, Raquel
author_role author
author2 Fairbanks, Lynette D.
Jinnah, H. A.
Guelbert, Norberto Bernardo
Escuredo, Emilia
Becerra, Adriana Berónica
Dodelson de Kremer, Raquel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Hypoxanthine-guanine phosphoribosyltransferase deficiency
Hyperuricemia
Lesch-Nyhan disease
Lesch-Nyhan variant
topic Hypoxanthine-guanine phosphoribosyltransferase deficiency
Hyperuricemia
Lesch-Nyhan disease
Lesch-Nyhan variant
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.
Fil: Laróvere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fairbanks, Lynette D.. Purine Research Laboratory, St. Thomass Hosp; Reino Unido
Fil: Jinnah, H. A.. University of Emory; Estados Unidos
Fil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Escuredo, Emilia. Purine Research Laboratory, St. Thomass Hosp; Reino Unido
Fil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
description Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.
publishDate 2021
dc.date.none.fl_str_mv 2021-03
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/11336/150718
Laróvere, Laura Elena; Fairbanks, Lynette D.; Jinnah, H. A.; Guelbert, Norberto Bernardo; Escuredo, Emilia; et al.; Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients; Scielo; Journal of Inborn Errors of Metabolism and Screening; 3-2021
2326-4594
CONICET Digital
CONICET
url http://hdl.handle.net/11336/150718
identifier_str_mv Laróvere, Laura Elena; Fairbanks, Lynette D.; Jinnah, H. A.; Guelbert, Norberto Bernardo; Escuredo, Emilia; et al.; Lesch-Nyhan disease and its variants: Phenotypic and mutation spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase deficiency in Argentine patients; Scielo; Journal of Inborn Errors of Metabolism and Screening; 3-2021
2326-4594
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1590/2326-4594-jiems-2020-0027
info:eu-repo/semantics/altIdentifier/url/https://www.scielo.br/j/jiems/a/bJKcpfbPCzLKSNMCqcHBGqD/?lang=en
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 Scielo
publisher.none.fl_str_mv Scielo
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 13.070432

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