Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency.
J Endocrinol Invest
; 38(4): 407-12, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25352235
ABSTRACT
PURPOSE:
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.CONCLUSION:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Infant, Small for Gestational Age
/
Glycoproteins
/
Carrier Proteins
/
Laron Syndrome
/
Growth Disorders
Limits:
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Endocrinol Invest
Year:
2015
Document type:
Article
Affiliation country:
Reino Unido