Acid-labile subunit deficiency and growth failure: description of two novel cases.
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David A, Rose SJ, Miraki-Moud F, Metherell LA, Savage MO, Clark AJ, Camacho-Hubner C
Acid-labile subunit deficiency and growth failure: description of two novel cases.
Horm Res Paediatr. 2010;73(5):328-34. doi: 10.1159/000308164. Epub 2010 Apr 14.
- PubMed ID
- 20389102 [ View in PubMed]
- Abstract
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.