BACKGROUND: Primary growth hormone insensitivity (GHI) and triple A syndrome are rare autosomal recessive disorders. CASE REPORT: The patient, a 12-year-old boy from consanguineous parents, was referred for short stature at the age of 7 years (height: -5.4 SD score). He had low serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 and a blunted IGF-I response to recombinant human GH; molecular analysis of the GH receptor disclosed a homozygous A(-1)→G(-1) at the 5' pseudoexon 6Ψ splice site. Recombinant IGF-I therapy (mecasermin, Increlex®, twice daily) initiated at the age of 9 years resulted in an increase of height velocity (HV) from 4.0 to 9.5 cm/year. At the age of 10.5 years, he presented with asthenia, anorexia, weight loss, a decrease in HV and very low cortisol levels; adrenal insufficiency was confirmed and glucocorticoid therapy was initiated. Subsequent peripheral motor neuropathy, achalasia and alacrima raised the suspicion of triple A syndrome, which was confirmed by the presence of a homozygous R194X mutation in the AAAS gene. CONCLUSION: This unusual combination of diseases, to our knowledge, has not been reported to date. Although the patient responded to recombinant IGF-I therapy for GHI, we hypothesize that the treatment could have had an inhibitory effect on 11β-hydroxysteroid dehydrogenase type 1 activity, thereby reducing the availability of cortisol and precipitating adrenal insufficiency.
BACKGROUND: Primary growth hormone insensitivity (GHI) and triple A syndrome are rare autosomal recessive disorders. CASE REPORT: The patient, a 12-year-old boy from consanguineous parents, was referred for short stature at the age of 7 years (height: -5.4 SD score). He had low serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 and a blunted IGF-I response to recombinant human GH; molecular analysis of the GH receptor disclosed a homozygous A(-1)→G(-1) at the 5' pseudoexon 6Ψ splice site. Recombinant IGF-I therapy (mecasermin, Increlex®, twice daily) initiated at the age of 9 years resulted in an increase of height velocity (HV) from 4.0 to 9.5 cm/year. At the age of 10.5 years, he presented with asthenia, anorexia, weight loss, a decrease in HV and very low cortisol levels; adrenal insufficiency was confirmed and glucocorticoid therapy was initiated. Subsequent peripheral motor neuropathy, achalasia and alacrima raised the suspicion of triple A syndrome, which was confirmed by the presence of a homozygous R194X mutation in the AAAS gene. CONCLUSION: This unusual combination of diseases, to our knowledge, has not been reported to date. Although the patient responded to recombinant IGF-I therapy for GHI, we hypothesize that the treatment could have had an inhibitory effect on 11β-hydroxysteroid dehydrogenase type 1 activity, thereby reducing the availability of cortisol and precipitating adrenal insufficiency.
Authors: David R Adams; Hongjie Yuan; Todd Holyoak; Katrina H Arajs; Parvin Hakimi; Thomas C Markello; Lynne A Wolfe; Thierry Vilboux; Barbara K Burton; Karin Fuentes Fajardo; George Grahame; Conisha Holloman; Murat Sincan; Ann C M Smith; Gordon A Wells; Yan Huang; Hugo Vega; James P Snyder; Gretchen A Golas; Cynthia J Tifft; Cornelius F Boerkoel; Richard W Hanson; Stephen F Traynelis; Douglas S Kerr; William A Gahl Journal: Mol Genet Metab Date: 2014-04-13 Impact factor: 4.797
Authors: Dennis Lal; Bernd A Neubauer; Mohammad R Toliat; Janine Altmüller; Holger Thiele; Peter Nürnberg; Clemens Kamrath; Anne Schänzer; Thomas Sander; Andreas Hahn; Michael Nothnagel Journal: PLoS One Date: 2016-01-20 Impact factor: 3.240