The role of acid-labile subunit (ALS) in the modulation of GH-IGF-I action

Mol Cell Endocrinol. 2020 Dec 1:518:111006. doi: 10.1016/j.mce.2020.111006. Epub 2020 Aug 27.


Acid-labile subunit (ALS) deficiency (ACLSD) constitutes the first monogenic defect involving a member of the Insulin-like Growth Factor (IGF) binding protein system. The lack of ALS completely disrupts the circulating IGF system. Autocrine/paracrine action of local produced IGF-I could explain the mild effect on growth. In the present work we have revised the more relevant clinical and biochemical consequences of complete ACLSD in 61 reported subjects from 31 families. Low birth weight and/or length, reduced head circumference, height between -2 and -3 SD, pubertal delay and insulin resistance are commonly observed. Partial ACLSD could be present in children initially labeled as idiopathic short stature, presenting low IGF-I levels, suggesting that one functional IGFALS allele is insufficient to stabilize ternary complexes. Dysfunction of the GH-IGF axis observed in ACLSD may eventually result in increased risk for type-2 diabetes and tumor progression. Consequently, long term surveillance is recommended in these patients.

Keywords: ALS deficiency; GH action; GH insensitivity; IGF-I deficiency; IGFALS gene; Short stature.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Body Height / drug effects
  • Body Height / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Child
  • Female
  • Glycoproteins / deficiency
  • Glycoproteins / genetics
  • Glycoproteins / pharmacology
  • Glycoproteins / physiology*
  • Growth Disorders / genetics
  • Growth Disorders / metabolism
  • Human Growth Hormone / metabolism*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Puberty, Delayed / genetics
  • Puberty, Delayed / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Carrier Proteins
  • Glycoproteins
  • IGF1 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • insulin-like growth factor binding protein, acid labile subunit
  • Human Growth Hormone
  • Insulin-Like Growth Factor I