1. Clinical features of a new acid-labile subunit (IGFALS) heterozygous mutation: anthropometric and biochemical characterization and response to growth hormone administration
- Author
-
GRANDONE, Anna, MIRAGLIA DEL GIUDICE, Emanuele, Cirillo G, ABBONDANZA, Ciro, CIOFFI, Michele, Romano T, Micillo F, Marzuillo P, PERRONE, Laura, Grandone, Anna, MIRAGLIA DEL GIUDICE, Emanuele, Cirillo, G, Abbondanza, Ciro, Cioffi, Michele, Romano, T, Micillo, F, Marzuillo, P, and Perrone, Laura
- Subjects
Heterozygote ,Endocrinology, Diabetes and Metabolism ,Dwarfism ,Endocrinology ,Child Development ,Growth hormone treatment ,Humans ,Body Weights and Measures ,Child ,Children ,GH and growth factor ,Glycoproteins ,Human Growth Hormone ,Medicine (all) ,Body Weights and Measure ,Pedigree ,Short stature ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Mutation ,Female ,Acid-labile subunit ,Glycoprotein ,Carrier Protein ,Carrier Proteins ,Human - Abstract
Background: Homozygous mutations in acid-labile subunit (IGFALS) gene result in short stature, very low circulating levels of acid-labile subunit (ALS), insulin growth factor 1 (IGF1) and insulin growth factor binding protein 3 (IGFBP3) and a poor response to growth hormone (GH). The impact of IGFALS mutations heterozygosity on growth is unknown. Patient and Methods: We describe a 10-year-old girl with severe short stature (height -3.2 SDS), heterozygous for a new IGFALS mutation. Results: The girl showed low circulating IGF1, IGFBP3 and ALS levels and normal GH secretion. We found a novel heterozygous frameshift IGFALS mutation (c.1283delA, p.Gln428Argfs*14). Size-exclusion chromatography showed a reduction of the IGF1, IGFBP3 and ALS 150-kDa ternary complex (by about 55%) compared to a control. An IGF-1 generation test, with two different GH dosages, showed a good response in term of increase in IGF1 and in formation of the ternary complex at size-exclusion chromatography. Clinical response after 6 months of therapy with GH was satisfactory (height velocity increased from 3 to 8 cm/year). Conclusion: We suggest that (1) heterozygous IGFALS mutations can be responsible for a subset of patients with severe short stature (below -2.5 SDS), low IGF1 (below -2 SDS) and normal GH secretion, and (2) the identification by IGFALS molecular screening of this subset of patients could help in the administration of the appropriate therapy. Background: Homozygous mutations in acid-labile subunit (IGFALS) gene result in short stature, very low circulating levels of acid-labile subunit (ALS), insulin growth factor 1 (IGF1) and insulin growth factor binding protein 3 (IGFBP3) and a poor response to growth hormone (GH). The impact of IGFALS mutations heterozygosity on growth is unknown. Patient and Methods: We describe a 10-year-old girl with severe short stature (height -3.2 SDS), heterozygous for a new IGFALS mutation. Results: The girl showed low circulating IGF1, IGFBP3 and ALS levels and normal GH secretion. We found a novel heterozygous frameshift IGFALS mutation (c.1283delA, p.Gln428Argfs*14). Size-exclusion chromatography showed a reduction of the IGF1, IGFBP3 and ALS 150-kDa ternary complex (by about 55%) compared to a control. An IGF-1 generation test, with two different GH dosages, showed a good response in term of increase in IGF1 and in formation of the ternary complex at size-exclusion chromatography. Clinical response after 6 months of therapy with GH was satisfactory (height velocity increased from 3 to 8 cm/year). Conclusion: We suggest that (1) heterozygous IGFALS mutations can be responsible for a subset of patients with severe short stature (below -2.5 SDS), low IGF1 (below -2 SDS) and normal GH secretion, and (2) the identification by IGFALS molecular screening of this subset of patients could help in the administration of the appropriate therapy. © 2013 S. Karger AG, Basel.
- Published
- 2013