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 language | English (US) |
|---|---|
| Pages (from-to) | 63-68 |
| Number of pages | 6 |
| Journal | Hormone Research in Paediatrics |
| Volume | 77 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2012 |
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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
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 journal › Article
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TY - JOUR
T1 - Triple a syndrome in a patient with genetic growth hormone insensitivity
T2 - Phenotypic effects of two genetic disorders
AU - Marín, Silvia
AU - Casano-Sancho, Paula
AU - Villarreal-Pena, Nancy
AU - Sebastiani, Giorgia
AU - Pinillos, Sergio
AU - Pérez-Duenas, Belén
AU - Hwa, Vivian
AU - Rosenfeld, Ronald (Ron)
AU - Ibánez, Lourdes
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Adrenal insufficiency
KW - Cortisol
KW - Growth
KW - Growth hormone insensitivity
KW - Insulin-like growth factor I
KW - Triple A syndrome
UR - http://www.scopus.com/inward/record.url?scp=84857366754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857366754&partnerID=8YFLogxK
U2 - 10.1159/000335235
DO - 10.1159/000335235
M3 - Article
VL - 77
SP - 63
EP - 68
JO - Hormone Research in Paediatrics
JF - Hormone Research in Paediatrics
SN - 1663-2818
IS - 1
ER -