Background: We recently reported three children with severe isolated growth hormone (GH) deficiency and pituitary hypoplasia due to biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein formation and splicing of U12-type introns. Although it is clear that these patients are GH deficient, the underlying mechanism for this deficit is not totally understood.
Objective: We aimed to analyze the effect of recombinant human GH (rhGH) therapy in the first three patients identified with this condition.
Results: Three sisters with extremely short stature and phenotypical features of severe GH deficiency due to compound heterozygous mutations in RNPC3 were studied. They were siblings from a Romanian family with parents of normal stature. Treatment with rhGH (0.0250.035 mg/kg/day) was initiated at 15.5, 8.1 and 6.0 years of age, with heights at onset of −5.9, −5.0 and −6.7 height-SDS, respectively. The eldest sister achieved adult height within her familial target, continuing to respond to treatment until 20 years of age when GH was discontinued. Her body fat content normalized and bone mineral density and trabecular bone structure significantly improved after 4.5 years on therapy. The two younger sisters are showing an even better response to rhGH after 6.5 years, with no side effects.
Conclusion: Long-term treatment with rhGH in patients with GH deficiency (GHD) due to RNPC3 mutations dramatically improves growth, bone mass, bone microarchitecture, and body composition, with no side effects.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology