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Updated: Jun 13, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Acid-labile subunit deficiency and growth failure: description of two novel cases
A David1, S J Rose, F Miraki-Moud
1Centre for Endocrinology, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.
Background/Aims:
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. Whether severe pubertal delay is also part of the phenotype remains controversial due to the small number of cases reported. We report 2 children with a history of growth failure due to novel IGFALS mutations.
Methods:
The growth hormone receptor gene (GHR) and IGFALS were analyzed by direct sequencing. Ternary complex formation was studied by size exclusion chromatography.
Results:
Two boys of 13.3 and 10.6 years, with pubertal stages 2 and 1, had mild short stature (-3.2 and -2.8 SDS, respectively) and a biochemical profile suggestive of growth hormone resistance. No defects were identified in the GHR. Patient 1 was homozygous for the IGFALS missense mutation P73L. Patient 2 was a compound heterozygote for the missense mutation L134Q and a novel GGC to AG substitution at position 546-548 (546-548delGGCinsAG). The latter causes a frameshift and the appearance of a premature stop codon. Size exclusion chromatography showed no peaks corresponding to ternary and binary complexes in either patient.
Conclusion:
Screening of the IGFALS is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS.
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