Human acid-labile subunit deficiency

Clinical, endocrine and metabolic consequences

Horacio M. Domené, Vivian Hwa, Jesús Argente, Jan M. Wit, Cecilia Camacho-Hübner, Héctor G. Jasper, Jesús Pozo, Hermine A. Van Duyvenvoorde, Shoshana Yakar, Olga V. Fofanova-Gambetti, Ron G. Rosenfeld

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)129-141
Number of pages13
JournalHormone Research
Volume72
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 5
Acids
Insulin-Like Growth Factor II
Growth
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Protein Subunits
Somatomedins
Puberty
Serum
Bone Density
Growth Hormone
Half-Life
Insulin
Mutation
Genes

Keywords

  • Acid-labile subunit
  • Growth hormone insensitivity
  • IGFALS gene mutations
  • Insulin insensitivity
  • Insulin-like growth factor binding protein
  • Insulin-like growth factor-I

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Domené, H. M., Hwa, V., Argente, J., Wit, J. M., Camacho-Hübner, C., Jasper, H. G., ... Rosenfeld, R. G. (2009). Human acid-labile subunit deficiency: Clinical, endocrine and metabolic consequences. Hormone Research, 72(3), 129-141. https://doi.org/10.1159/000232486

Human acid-labile subunit deficiency : Clinical, endocrine and metabolic consequences. / Domené, Horacio M.; Hwa, Vivian; Argente, Jesús; Wit, Jan M.; Camacho-Hübner, Cecilia; Jasper, Héctor G.; Pozo, Jesús; Van Duyvenvoorde, Hermine A.; Yakar, Shoshana; Fofanova-Gambetti, Olga V.; Rosenfeld, Ron G.

In: Hormone Research, Vol. 72, No. 3, 09.2009, p. 129-141.

Research output: Contribution to journalArticle

Domené, HM, Hwa, V, Argente, J, Wit, JM, Camacho-Hübner, C, Jasper, HG, Pozo, J, Van Duyvenvoorde, HA, Yakar, S, Fofanova-Gambetti, OV & Rosenfeld, RG 2009, 'Human acid-labile subunit deficiency: Clinical, endocrine and metabolic consequences', Hormone Research, vol. 72, no. 3, pp. 129-141. https://doi.org/10.1159/000232486
Domené HM, Hwa V, Argente J, Wit JM, Camacho-Hübner C, Jasper HG et al. Human acid-labile subunit deficiency: Clinical, endocrine and metabolic consequences. Hormone Research. 2009 Sep;72(3):129-141. https://doi.org/10.1159/000232486
Domené, Horacio M. ; Hwa, Vivian ; Argente, Jesús ; Wit, Jan M. ; Camacho-Hübner, Cecilia ; Jasper, Héctor G. ; Pozo, Jesús ; Van Duyvenvoorde, Hermine A. ; Yakar, Shoshana ; Fofanova-Gambetti, Olga V. ; Rosenfeld, Ron G. / Human acid-labile subunit deficiency : Clinical, endocrine and metabolic consequences. In: Hormone Research. 2009 ; Vol. 72, No. 3. pp. 129-141.
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