title: Short stature and metabolic abnormalities in two sisters with a 7.6-kb GH1 gene deletion.
abstract: Growth hormone 1 (GH1) gene deletions occur in approximately 10-15% of patients with severe isolated, GH deficiency (GHD). The standard treatment for GHD is GH replacement. Individuals with GH gene defects, however, may form GH antibodies that interfere with the efficacy of exogenous recombinant GH (rhGH) therapy.
  
  
  OBJECTIVE
  We describe the growth measures and metabolic studies of two Hispanic sisters with the same 7.6-kb GH1 gene deletion who presented with short stature and increased body fat, and who developed neutralizing GH antibodies secondary to rhGH exposure.
  
  
  METHODS
  The younger sister has now been treated with recombinant human insulin-like growth factor-I (rhIGF-I) for 4 years, and is continuing treatment. The older sister was not given rhIGF-I based on her normal height velocity and age. After the first 4 years of rhIGF-I treatment of the younger sister, we summarized the longitudinal anthropometric measures and serial laboratory studies, including GH surrogates, fasting lipid studies, oral glucose tolerance tests, and HbA1c, of both sisters. Body composition was quantified using DEXA analysis.
  
  
  RESULTS
  The older sister achieved an adult stature at the low end of her mid-parental target height range, having been treated only with rhGH for ~2.5 years (between 11 months and 3.5 years of age). Treatment of the younger sister with rhIGF-I for 4 years has led to persistent improvement in height velocity, but was associated with adverse short-term effects on all lipids. Her BMI increased modestly (+4.1 kg/m(2)) during rhIGF-I treatment, though her change in percent body fat was negligible by DEXA (Δ -0.7%).
  
  
  CONCLUSIONS
  In individuals with a GH gene deletion, rhIGF-I promotes increased height velocity, but may be associated with adverse effects on lipids and BMI. It is clear that the long-term effects of rhIGF-I on lipid metabolism and body composition require further monitoring and assessment with continued treatment.
authors.affiliation: Center for Endocrinology, Diabetes, and Metabolism, Childrens Hospital Los Angeles, Los Angeles, CA, USA. tahmad@mail.cho.org
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.forename: Mitchell
authors.initials: M
authors.lastname: Geffner
authors.forename: John
authors.initials: J
authors.lastname: Parks
authors.forename: Milton
authors.initials: M
authors.lastname: Brown
authors.forename: Lynda
authors.initials: L
authors.lastname: Fisher
authors.forename: Gertrude
authors.initials: G
authors.lastname: Costin
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000502:physiology; D002648:Child; D005260:Female; D017353:Gene Deletion; D006130:Growth Disorders / Q000150:complications* / Q000235:genetics*; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008659:Metabolic Diseases / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D035781:Siblings; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone