The proband, an 8.7 years female with pre- and postnatal growth failure (BW SDS -3.04, Ht SDS -3.86) and biochemical features of GHI, had a homozygous mutation of IGFALS, c.401T>A; p.L134Q.
Children with homozygous mutations of IGFALS have a low or normal birth weight, a mild growth failure, a head circumference in the lower normal range, and no failure to thrive.
Homozygous IGFALS defects are relatively common, and lead to moderate growth failure, very low serum IGF-1 and even lower IGFBP-3, while a heterozygous IGFALS mutation decreases height by 1 SD.
A small number of children (to date 10) with modest growth failure and in the majority delayed puberty, a phenotype similar to that of CDGP, have been reported to carry mutations in the IGF acid labile subunit (IGFALS) gene which encodes the ALS, a part of the ternary complex carrying IGF-I in the circulation.