Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences

Autores
Domene, Horacio Mario; Hwa, Vivian; Argente, Jesús; Wit, Jan M.; Camacho Hübner, Cecilia; Jasper, Hector Guillermo; Pozo, Jesús; van Duyvenvoorde, Hermine; Yakar, Shoshana; Fofanova-Gambetti, Olga V.; Rosenfeld, Ron G.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting that ALS deficiency may be prevalent in a subset of patients with extraordinarily low serum levels of IGF-I and IGFBP-3 that remain abnormally low upon growth hormone stimulation. Postnatal growth was clearly affected. Commonly, the height standard deviation score before puberty was between –2 and –3, and approximately 1.4 SD shorter than the midparental height SDS. Pubertal delay was found in 50% of the patients. Circulating IGF-II, IGFBP-1, -2 and -3 levels were reduced, with the greatest reduction observed for IGFBP-3. Insulin insensitivity was a common finding, and some patients presented low bone mineral density. Human ALS deficiency represents a unique condition in which the lack of ALS proteins results in the disruption of the entire IGF circulating system. Despite a profound circulating IGF-I deficiency, there is only a mild impact on postnatal growth. The preserved expression of locally produced IGF-I might be responsible for the preservation of linear growth near normal limits.
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Hwa, Vivian. University of Oregon; Estados Unidos
Fil: Argente, Jesús. Universidad Autónoma de Madrid; España
Fil: Wit, Jan M.. No especifíca;
Fil: Camacho Hübner, Cecilia. No especifíca;
Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Pozo, Jesús. Universidad Autónoma de Madrid; España
Fil: van Duyvenvoorde, Hermine. No especifíca;
Fil: Yakar, Shoshana. No especifíca;
Fil: Fofanova-Gambetti, Olga V.. University of Oregon; Estados Unidos
Fil: Rosenfeld, Ron G.. University of Oregon; Estados Unidos
Materia
ACID-LABILE SUBUNIT
GROWTH HORMONE INSENSITIVITY
IGFALS GENE MUTATIONS
INSULIN INSENSITIVITY
INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN
INSULIN-LIKE GROWTH FACTOR-I
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:11336/159906
Acceder
id CONICETDig_c5959c3ca996c81b6eeb13148b36ea47
oai_identifier_str oai:ri.conicet.gov.ar:11336/159906
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic ConsequencesDomene, Horacio MarioHwa, VivianArgente, JesúsWit, Jan M.Camacho Hübner, CeciliaJasper, Hector GuillermoPozo, Jesúsvan Duyvenvoorde, HermineYakar, ShoshanaFofanova-Gambetti, Olga V.Rosenfeld, Ron G.ACID-LABILE SUBUNITGROWTH HORMONE INSENSITIVITYIGFALS GENE MUTATIONSINSULIN INSENSITIVITYINSULIN-LIKE GROWTH FACTOR BINDING PROTEININSULIN-LIKE GROWTH FACTOR-Ihttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting that ALS deficiency may be prevalent in a subset of patients with extraordinarily low serum levels of IGF-I and IGFBP-3 that remain abnormally low upon growth hormone stimulation. Postnatal growth was clearly affected. Commonly, the height standard deviation score before puberty was between –2 and –3, and approximately 1.4 SD shorter than the midparental height SDS. Pubertal delay was found in 50% of the patients. Circulating IGF-II, IGFBP-1, -2 and -3 levels were reduced, with the greatest reduction observed for IGFBP-3. Insulin insensitivity was a common finding, and some patients presented low bone mineral density. Human ALS deficiency represents a unique condition in which the lack of ALS proteins results in the disruption of the entire IGF circulating system. Despite a profound circulating IGF-I deficiency, there is only a mild impact on postnatal growth. The preserved expression of locally produced IGF-I might be responsible for the preservation of linear growth near normal limits.Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Hwa, Vivian. University of Oregon; Estados UnidosFil: Argente, Jesús. Universidad Autónoma de Madrid; EspañaFil: Wit, Jan M.. No especifíca;Fil: Camacho Hübner, Cecilia. No especifíca;Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Pozo, Jesús. Universidad Autónoma de Madrid; EspañaFil: van Duyvenvoorde, Hermine. No especifíca;Fil: Yakar, Shoshana. No especifíca;Fil: Fofanova-Gambetti, Olga V.. University of Oregon; Estados UnidosFil: Rosenfeld, Ron G.. University of Oregon; Estados UnidosKarger2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/159906Domene, Horacio Mario; Hwa, Vivian; Argente, Jesús; Wit, Jan M.; Camacho Hübner, Cecilia; et al.; Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences; Karger; Hormone Research; 72; 3; 12-2009; 129-1410301-0163CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1159/000232486info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:46:00Zoai:ri.conicet.gov.ar:11336/159906instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:46:01.14CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
title Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
spellingShingle Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
Domene, Horacio Mario
ACID-LABILE SUBUNIT
GROWTH HORMONE INSENSITIVITY
IGFALS GENE MUTATIONS
INSULIN INSENSITIVITY
INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN
INSULIN-LIKE GROWTH FACTOR-I
title_short Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
title_full Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
title_fullStr Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
title_full_unstemmed Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
title_sort Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
dc.creator.none.fl_str_mv Domene, Horacio Mario
Hwa, Vivian
Argente, Jesús
Wit, Jan M.
Camacho Hübner, Cecilia
Jasper, Hector Guillermo
Pozo, Jesús
van Duyvenvoorde, Hermine
Yakar, Shoshana
Fofanova-Gambetti, Olga V.
Rosenfeld, Ron G.
author Domene, Horacio Mario
author_facet Domene, Horacio Mario
Hwa, Vivian
Argente, Jesús
Wit, Jan M.
Camacho Hübner, Cecilia
Jasper, Hector Guillermo
Pozo, Jesús
van Duyvenvoorde, Hermine
Yakar, Shoshana
Fofanova-Gambetti, Olga V.
Rosenfeld, Ron G.
author_role author
author2 Hwa, Vivian
Argente, Jesús
Wit, Jan M.
Camacho Hübner, Cecilia
Jasper, Hector Guillermo
Pozo, Jesús
van Duyvenvoorde, Hermine
Yakar, Shoshana
Fofanova-Gambetti, Olga V.
Rosenfeld, Ron G.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACID-LABILE SUBUNIT
GROWTH HORMONE INSENSITIVITY
IGFALS GENE MUTATIONS
INSULIN INSENSITIVITY
INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN
INSULIN-LIKE GROWTH FACTOR-I
topic ACID-LABILE SUBUNIT
GROWTH HORMONE INSENSITIVITY
IGFALS GENE MUTATIONS
INSULIN INSENSITIVITY
INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN
INSULIN-LIKE GROWTH FACTOR-I
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting that ALS deficiency may be prevalent in a subset of patients with extraordinarily low serum levels of IGF-I and IGFBP-3 that remain abnormally low upon growth hormone stimulation. Postnatal growth was clearly affected. Commonly, the height standard deviation score before puberty was between –2 and –3, and approximately 1.4 SD shorter than the midparental height SDS. Pubertal delay was found in 50% of the patients. Circulating IGF-II, IGFBP-1, -2 and -3 levels were reduced, with the greatest reduction observed for IGFBP-3. Insulin insensitivity was a common finding, and some patients presented low bone mineral density. Human ALS deficiency represents a unique condition in which the lack of ALS proteins results in the disruption of the entire IGF circulating system. Despite a profound circulating IGF-I deficiency, there is only a mild impact on postnatal growth. The preserved expression of locally produced IGF-I might be responsible for the preservation of linear growth near normal limits.
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Hwa, Vivian. University of Oregon; Estados Unidos
Fil: Argente, Jesús. Universidad Autónoma de Madrid; España
Fil: Wit, Jan M.. No especifíca;
Fil: Camacho Hübner, Cecilia. No especifíca;
Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Pozo, Jesús. Universidad Autónoma de Madrid; España
Fil: van Duyvenvoorde, Hermine. No especifíca;
Fil: Yakar, Shoshana. No especifíca;
Fil: Fofanova-Gambetti, Olga V.. University of Oregon; Estados Unidos
Fil: Rosenfeld, Ron G.. University of Oregon; Estados Unidos
description The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting that ALS deficiency may be prevalent in a subset of patients with extraordinarily low serum levels of IGF-I and IGFBP-3 that remain abnormally low upon growth hormone stimulation. Postnatal growth was clearly affected. Commonly, the height standard deviation score before puberty was between –2 and –3, and approximately 1.4 SD shorter than the midparental height SDS. Pubertal delay was found in 50% of the patients. Circulating IGF-II, IGFBP-1, -2 and -3 levels were reduced, with the greatest reduction observed for IGFBP-3. Insulin insensitivity was a common finding, and some patients presented low bone mineral density. Human ALS deficiency represents a unique condition in which the lack of ALS proteins results in the disruption of the entire IGF circulating system. Despite a profound circulating IGF-I deficiency, there is only a mild impact on postnatal growth. The preserved expression of locally produced IGF-I might be responsible for the preservation of linear growth near normal limits.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
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/11336/159906
Domene, Horacio Mario; Hwa, Vivian; Argente, Jesús; Wit, Jan M.; Camacho Hübner, Cecilia; et al.; Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences; Karger; Hormone Research; 72; 3; 12-2009; 129-141
0301-0163
CONICET Digital
CONICET
url http://hdl.handle.net/11336/159906
identifier_str_mv Domene, Horacio Mario; Hwa, Vivian; Argente, Jesús; Wit, Jan M.; Camacho Hübner, Cecilia; et al.; Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences; Karger; Hormone Research; 72; 3; 12-2009; 129-141
0301-0163
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1159/000232486
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
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 13.22299

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