These findings suggest that heterozygous IGFALS gene variants could be responsible for short stature in a subset of ISS children with diminished levels of IGF-1, IGFBP-3 and ALS.
Mutations in the acid-labile subunit (ALS) gene (IGFALS) have been associated with circulating insulin-like growth factor I (IGF-I) deficiency and short stature.
The observation that in families of ALS deficient patients, heterozygous carriers for IGFALS gene mutations are shorter than their wild type relatives and the relatively high frequency of heterozygosity for this gene in children with idiopathic short stature suggests a requirement of normal levels of ALS for the attainment of maximal growth potential.