CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Type-IA Isolated Growth Hormone Deficiency (IGHD) Resulting from Compound
Autor/es:
A. KESELMAN; P. SCAGLIA; S. RODRÍGUEZ; M.G. BALLERINI; M.E. RODRÍGUEZ; M.G. ROPELATO; I. BERGADÁ; H.G. JASPER; H.M. DOMENÉ
Lugar:
Cartagena de Indias
Reunión:
Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011
Institución organizadora:
Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)
Resumen:
Type-IA Isolated Growth Hormone Deficiency (IGHD) Resulting from Compound Heterozygous Deletion of 6.7 and 7.6 Kb at the GH1 Gene Locus A. Keselman, P. Scaglia, S. Rodríguez, M.G. Ballerini,M.E. Rodríguez, M.G. Ropelato, I. Bergadá, H.G. Jasper, H.M. Domené Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), División de Endocrinología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina Introduction: IGHD may result from deletion/mutations in the GH1 gene. Objective: to characterize the molecular defect in a girl presenting IGHD. Methods: The patient was born at 41 weeks of gestation from non-consanguineous parents. Clinical and biochemical evaluation included anthropometric measurements, arginine stimulation tests, IGF-I and IGFBP-3 levels. Molecular characterization included PCR amplification of GH1 gene and SmaI digestion of two homologous flanking fragments, using genomic DNA from the patient and her parents as templates. Results: At 1.8 years of age the patient presented severe growth retardation, trunk obesity, frontal bossing, puppet-like face and acromicria. MRI showed pituitary hypoplasia. Laboratory findings confirmed IGHD (Table). GH1 gene did not amplified by PCR in samples from the patient (suggestive of gene deletion), while her parents showed one band of the expected size. SmaI digestion was compatible with the patient being a compound heterozygous for 6.7 and 7.6 Kb deletions, while her parents appear to be heterozygous carriers for either the 6.7 or the 7.6 Kb deletions. Conclusion: We have characterized type-IA IGHD caused by compound heterozygosity for two different GH1 gene deletions, suggesting that this condition should be suspected in severe IGHD, even in non-consanguineous families.     Auxological evaluation At birth 10 months 1.8 years Height, cm (SDS) 44 (-3,7) 57 (-5.9) 61.2 (-7.4) Weight, g (SDS) 2460 (-2.0) 5100 (-3.6) 6680 (-3.7) Head circumference, cm (SDS) 34.1   42.1 (-2.0) 43.2 (<-2.0) Body proportions, cm (percentile)   37.0 (25th) 39.2 (25th)         Endocrinological evaluation at 1.8 years Value Reference values Prolactin (ng/ml) 21  3 - 15 Cortisol (mg/dl) 43 6 - 21 ACTH (pg/ml) 40 10 - 50 GHBP (nmol/L) 1.62 1.04 - 6.17 TSH (mUI/ml) 2.81 0.5 - 6.5 FT4 (ng/ml) 1.28 0.8 - 2.0 GH (ng/ml),  basal < 0.05 0.1 - 3.0                     maximal response post arginine < 0.05 > 6.0 IGF-I (ng/ml) < 25 56 - 140 IGFBP-3 (µg/ml) < 0.50 2,0 - 4,4