Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences

Horm Res. 2009;72(3):129-41. doi: 10.1159/000232486. Epub 2009 Sep 1.


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.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Birth Weight
  • Body Height / genetics
  • Bone and Bones / metabolism
  • Calcification, Physiologic
  • Carbohydrate Metabolism
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Female
  • Frameshift Mutation
  • Glycoproteins / deficiency*
  • Glycoproteins / genetics
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mutation, Missense


  • Carrier Proteins
  • Glycoproteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • insulin-like growth factor binding protein, acid labile subunit
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II