Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium

Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/Methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type. Within each family, the effect of IGFALS mutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height sd score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was −2.31 ± 0.87 (less than −2 SDS in 62%); in 1ALS, −0.83 ± 1.34 (less than −2 SDS in 26%); and in WT, −...