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, Ronald (Ron) Rosenfeld, Lourdes Ibánez

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 2012

Fingerprint

Inborn Genetic Diseases
Insulin-Like Growth Factor I
Growth Hormone
Adrenal Insufficiency
Insulin-Like Growth Factor Binding Protein 3
Hydrocortisone
11-beta-Hydroxysteroid Dehydrogenases
Asthenia
Esophageal Achalasia
Anorexia
Peripheral Nervous System Diseases
Therapeutics
Glucocorticoids
Weight Loss
Parents
Mutation
Serum
Genes
mecasermin
Achalasia Addisonianism Alacrimia syndrome

Keywords

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

ASJC Scopus subject areas

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

Cite this

Marín, S., Casano-Sancho, P., Villarreal-Pena, N., Sebastiani, G., Pinillos, S., Pérez-Duenas, B., ... 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

Triple a syndrome in a patient with genetic growth hormone insensitivity : Phenotypic effects of two genetic disorders. / Marín, Silvia; Casano-Sancho, Paula; Villarreal-Pena, Nancy; Sebastiani, Giorgia; Pinillos, Sergio; Pérez-Duenas, Belén; Hwa, Vivian; Rosenfeld, Ronald (Ron); Ibánez, Lourdes.

In: Hormone Research in Paediatrics, Vol. 77, No. 1, 02.2012, p. 63-68.

Research output: Contribution to journalArticle

Marín, S, Casano-Sancho, P, Villarreal-Pena, N, Sebastiani, G, Pinillos, S, Pérez-Duenas, B, Hwa, V, Rosenfeld, RR & Ibánez, L 2012, 'Triple a syndrome in a patient with genetic growth hormone insensitivity: Phenotypic effects of two genetic disorders', Hormone Research in Paediatrics, vol. 77, no. 1, pp. 63-68. https://doi.org/10.1159/000335235
Marín S, Casano-Sancho P, Villarreal-Pena N, Sebastiani G, Pinillos S, Pérez-Duenas B et al. Triple a syndrome in a patient with genetic growth hormone insensitivity: Phenotypic effects of two genetic disorders. Hormone Research in Paediatrics. 2012 Feb;77(1):63-68. https://doi.org/10.1159/000335235
Marín, Silvia ; Casano-Sancho, Paula ; Villarreal-Pena, Nancy ; Sebastiani, Giorgia ; Pinillos, Sergio ; Pérez-Duenas, Belén ; Hwa, Vivian ; Rosenfeld, Ronald (Ron) ; Ibánez, Lourdes. / Triple a syndrome in a patient with genetic growth hormone insensitivity : Phenotypic effects of two genetic disorders. In: Hormone Research in Paediatrics. 2012 ; Vol. 77, No. 1. pp. 63-68.
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