title: Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency.
abstract: OBJECTIVE
  The IGFALS gene encodes the acid-labile subunit (ALS) protein, which regulates circulating IGF-1. Human IGFALS mutations cause growth hormone insensitivity (GHI) associated with ALS, IGF-1 and IGFBP-3 deficiencies and mild to moderate postnatal growth impairment (height SDS -2 to -4). Prenatal growth impairment is not a recognised feature of this disorder, but heterozygous carriers may show an intermediate phenotype.
  
  
  METHODS
  We report a family of five subjects, including three children born small for gestational age, who were investigated for IGFALS gene mutations.
  
  
  RESULTS
  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. Her 6.1 years brother (BW SDS -2.11, Ht SDS -2.0) had the same homozygous IGFALS mutation. Both parents [adult height SDS -1.76 (father) and -1.82 (mother)] and her 2.7 years sister (BW SDS -2.60, Ht SDS -2.04) were heterozygous for the IGFALS mutation.
  
  
  CONCLUSIONS
  Significant phenotypic heterogeneity was observed between family members, in particular varying degrees of prenatal growth retardation were present in the three siblings, which may have contributed to the variation in the postnatal growth phenotype.
authors.affiliation: Centre for Endocrinology, John Vane Science Centre, William Harvey Research Institute (WHRI), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. h.l.storr@qmul.ac.uk.
authors.forename: H L
authors.initials: HL
authors.lastname: Storr
authors.affiliation: Centre for Endocrinology, John Vane Science Centre, William Harvey Research Institute (WHRI), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: I K
authors.initials: IK
authors.lastname: Temple
authors.affiliation: Centre for Endocrinology, John Vane Science Centre, William Harvey Research Institute (WHRI), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Metherell
authors.affiliation: Centre for Endocrinology, John Vane Science Centre, William Harvey Research Institute (WHRI), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
authors.affiliation: Department of Paediatric Endocrinology, Portsmouth Hospitals National Health Service Trust, Portsmouth, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Walker
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007236:Infant, Small for Gestational Age; D046150:Laron Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009679:Nuclear Family; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C075944:insulin-like growth factor binding protein, acid labile subunit
keywords: Acid-labile subunit (ALS); Growth hormone insensitivity (GHI); IGFALS mutation; Short stature; Small for gestational age (SGA)