Poster Presentation ESA-SRB-APEG-NZSE 2022

Three Year Follow Up of Two Siblings Treated with IGF-1 for Growth Hormone Insensitivity Syndrome due to a Novel Mutation of Intron 4 of the Growth Hormone Receptor (#453)

Mark Davidson 1 , Shihab Hameed 1 2 3 4 , Geoffrey Ambler 3 5 , Andreas Zankl 3 6 , Ken Peacock 7
  1. Paediatric Endocrinology, Sydney Children's Hospital, Sydney, NSW, Australia
  2. Paediatric Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia
  3. The University of Sydney, Sydney, NSW, Australia
  4. The University of New South Wales, Sydney, NSW, Australia
  5. Paediatric Endocrinology, The Children's Hospital Westmead, Sydney, NSW, Australia
  6. Clincial Genetics, The Children's Hospital Westmead, Sydney, NSW, Australia
  7. General Medicine, The Children's Hospital Westmead, Sydney, NSW, Australia

Growth hormone insensitivity syndrome (GHIS) results from absent/attenuated growth hormone response on its receptor (GHR). It causes severe post-natal growth failure, hypoglycaemia, and obesity, high circulating growth hormone and low insulin-like growth factor 1 (IGF-1). We present two female siblings (S1 and S2) with GHIS due to the same novel mutation of the GHR and their response to IGF-1 over the first 3 years of treatment. S1 had normal size at birth (weight 3.46kg (77th centile), length 45cm (2nd centile)), but developed severe early growth failure, and was referred to endocrinology at 6 months of age. She had high circulating GH (67.5mIU/L, RI 6-30) and low IGF-1 (< 2.0 nmolL, RI 7.0-43.3). IGF-1 generation testing for suspected GHIS was consistent with the diagnosis (Table 1). Genomic sequencing detected a novel mutation of intron 4 of the GHR (GHR c.266+68T>G) with a predicted frameshift and early protein termination. S2 also developed post-natal growth failure due to the same GHR mutation. Both girls were commenced on IGF-1 treatment (Mecasermin 150mcg/kg/day) as a once daily s.c. injection (Laron, 2014). Blood and interstitial glucose monitoring were instituted. Growth velocities of S1 and S2 improved from 5.8cm/year (3rd centile) to 9.3cm/year (>97th centile) and 3cm/year (<3rd centile) to 7.7cm/year (>50th centile), respectively. The parents reported an improvement in energy, strength and appetite. Over the 3 years of treatment to date there have been ongoing improvements in height z scores from -6.6 to -4.0 for S1 and from -6.3 to -4.7 for S2. Despite dietary precautions, weight has increased disproportionately consistent with the GHIS phenotype, with current BMIs of 22.6kg/m2 (98th centile) for S1 and 16.5kg/m2 (76th centile) for S2.  Hypoglycaemia has not increased on IGF-1 treatment.  These cases highlight the important benefits of IGF-1 and difficulties encountered in the management of children with GHIS.

 

62ff23e4abb96-Table+1.jpg

  1. 1. Laron, Z. (2014). Emerging treatment options for patients with Laron syndrome. Expert Opinion on Orphan Drugs 2(7).