Triple a syndrome in a patient with genetic growth hormone insensitivity: Phenotypic effects of two genetic disorders

Silvia Marín, Paula Casano-Sancho, Nancy Villarreal-Pena, Giorgia Sebastiani, Sergio Pinillos, Belén Pérez-Duenas, Vivian Hwa, Ron G. Rosenfeld, Lourdes Ibánez

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 Ψ pseudoexon 6 Ψ 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 11 β -hydroxysteroid dehydrogenase type 1 activity, thereby reducing the availability of cortisol and precipitating adrenal insufficiency.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalHormone Research in Paediatrics
Volume77
Issue number1
DOIs
StatePublished - Feb 1 2012

Keywords

  • Adrenal insufficiency
  • Cortisol
  • Growth
  • Growth hormone insensitivity
  • Insulin-like growth factor I
  • Triple A syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Marín, S., Casano-Sancho, P., Villarreal-Pena, N., Sebastiani, G., Pinillos, S., Pérez-Duenas, B., Hwa, V., Rosenfeld, R. G., & Ibánez, L. (2012). Triple a syndrome in a patient with genetic growth hormone insensitivity: Phenotypic effects of two genetic disorders. Hormone Research in Paediatrics, 77(1), 63-68. https://doi.org/10.1159/000335235