title: Clinical features of a new acid-labile subunit (IGFALS) heterozygous mutation: anthropometric and biochemical characterization and response to growth hormone administration.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.forename: Emanuele
authors.initials: E
authors.lastname: Miraglia del Giudice
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.forename: Ciro
authors.initials: C
authors.lastname: Abbondanza
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Romano
authors.forename: Flora
authors.initials: F
authors.lastname: Micillo
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Marzuillo
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
mesh_terms: D001837:Body Weights and Measures; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002657:Child Development / Q000187:drug effects; D004392:Dwarfism / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone