Different Growth Responses to Recombinant Human Growth Hormone in Three Siblings with Isolated Growth Hormone Deficiency Type 1A due to a 6.7Kb Deletion in the GH1 Gene
Open Access
- 1 December 2021
- journal article
- research article
- Published by Galenos Yayinevi in Journal of Clinical Research in Pediatric Endocrinology
- Vol. 13 (4), 456-460
- https://doi.org/10.4274/jcrpe.galenos.2020.2020.0005
Abstract
Isolated growth hormone deficiency (IGHD) type 1A is a rare, autosomal recessive disorder caused by deletion of the GH1 gene and characterized by early onset severe short stature and typical phenotype. Lack of exposure to GH during fetal life often leads to formation of anti-GH antibody following exposure even the least immunogenic recombinant human GH (rhGH). Some patients with circulating anti-GH antibodies demonstrate lack of growth response to GH while others do not. However, the clinical significance of this antibody is unclear; hence testing is not routinely recommended. Three siblings, born of a consanguineous union, were referred with severe short stature. They were evaluated and IGHD was diagnosed in all of them. Genetic analysis revealed that all three had homozygous 6.7 Kb deletion in GH1 gene, while their parents displayed a pattern of heterozygous 6.7 Kb deletions. rhGH was started at 10, 6 and 1.58 years of age, respectively. Growth and hormonal parameters were monitored throughout the course of treatment. The eldest sibling demonstrated expected growth velocity (9.5 cm/year) for the first year of rhGH that rapidly waned thereafter (2.5 cm/year). The youngest sibling experienced excellent growth response even after the third year (10.3 cm/year) while the middle sibling displayed sub-optimal response from rhGH initiation (6.3 cm/year). Change of rhGH brand did not work in the two elder sisters. Such a different growth response with rhGH in three siblings harbouring similar genetic abnormality has not been described previously.Keywords
This publication has 10 references indexed in Scilit:
- Biological Significance of Anti-GH Antibodies in Children Treated with rhGHHormone Research in Paediatrics, 2019
- Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomesEBioMedicine, 2018
- Genetics of ısolated growth hormone deficiencyJournal of Clinical Research in Pediatric Endocrinology, 2010
- Growth Hormone Antibodies Formation in Patients Treated with Recombinant Human Growth HormoneInternational Journal of Immunopathology and Pharmacology, 2004
- An Exon Splice Enhancer Mutation Causes Autosomal Dominant GH DeficiencyJournal of Clinical Endocrinology & Metabolism, 2002
- An Improved Polymerase Chain Reaction (PCR) Protocol for Unambigous Detection of Growth Hormone Gene DeletionsJournal of Pediatric Endocrinology and Metabolism, 1998
- Comparative Study of Biosynthetic Human Growth Hormone Immunogenicity in Growth Hormone Deficient ChildrenHormone Research, 1991
- Use of Polymerase Chain Reaction in Detection of Growth Hormone Gene Deletions*Journal of Clinical Endocrinology & Metabolism, 1990
- Human growth hormone gene deletion without antibody formation or growth arrest during treatment--a new disease entity?1985
- Phenotypic Heterogeneity in Familial Isolated Growth Hormone Deficiency Type I-A*Journal of Clinical Endocrinology & Metabolism, 1984