Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency

Purpose The IGFALS gene encodes the acid-labile subunit (ALS) protein, which regulates circulating IGF-1. Human IGFALS mutations cause growth hormone insensitivity (GHI) associated with ALS, IGF-1 and IGFBP-3 deficiencies and mild to moderate postnatal growth impairment (height SDS −2 to −4). Prenatal growth impairment is not a recognised feature of this disorder, but heterozygous carriers may show an intermediate phenotype.