Familial growth hormone deficiency with mutated GHRH receptor gene: Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha

César Y. Hayashida, Rogério G. Gondo, Carmela Ferrari, Sérgio P.A. Toledo, Roberto Salvatori, Michael A. Levine, Marilza C.L. Ezabella, Neusa Abelin, Daniel Gianella-Neto, Bernardo L. Wajchenberg

Research output: Contribution to journalArticle

Abstract

Objective: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. Design: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. Methods: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). Results: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) ± S.D.: -7.35 ± 1.37 vs -1.84 ± 1.44 respectively, P < 0.0001), and the wt/wt group (-1.85 ± 0.81, P = 0.0007). The height of the 13 wt/mt subjects did not differ from the 5 wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. Conclusions: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

Original languageEnglish (US)
Pages (from-to)557-563
Number of pages7
JournalEuropean journal of endocrinology
Volume142
Issue number6
DOIs
StatePublished - Jun 2000

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Familial growth hormone deficiency with mutated GHRH receptor gene: Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha'. Together they form a unique fingerprint.

  • Cite this

    Hayashida, C. Y., Gondo, R. G., Ferrari, C., Toledo, S. P. A., Salvatori, R., Levine, M. A., Ezabella, M. C. L., Abelin, N., Gianella-Neto, D., & Wajchenberg, B. L. (2000). Familial growth hormone deficiency with mutated GHRH receptor gene: Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha. European journal of endocrinology, 142(6), 557-563. https://doi.org/10.1530/eje.0.1420557