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 journalShort survey

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

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, Diabetes and Metabolism
  • Endocrinology

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  • Cite this

    Domené, H. M., Hwa, V., Argente, J., Wit, J. M., Camacho-Hübner, C., Jasper, H. G., Pozo, J., Van Duyvenvoorde, H. A., Yakar, S., Fofanova-Gambetti, O. V., & 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