ESPE Abstracts (2018) 89 P-P1-145

Response to Growth Hormone in Patients with Isolated Familial Growth Hormone Deficiency due to RNPC3 Mutations

Lourdes Travieso-Suáreza, Gabriel Martos-Morenoa,b,c,e, Jesús Pozoa,b,c,d, María Muñoz-Calvoa,b,c,d, Julie Chowena,b,c,e, Mikko Frilanderf, Luis Pérez-Juradog,h,i,j, Federico Hawkinsk,l & Jesús Argentea,b,c,d,e

aDepartments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; bLa Princesa Reasearch Institute, Madrid, Spain; cCentro de Investigación Biomédica en Red de Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; dUniversidad Autónoma de Madrid, Department of Pediatrics, Madrid, Spain; eIMDEA Food Institute, Madrid, Spain; fInstitute of Biotechnology, University of Helsinki, Helsinki, Finland; gGenetics Unit, Universitat Pompeu Fabra, Barcelona, Spain; hHospital del Mar Research Institute (IMIM), Barcelona, Spain; iCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain; jSA Clinical Genetics, Women’s and Children’s Hospital & University of Adelaide, Adelaide, Australia; kDiabetes and Bone Research Center, Institute i+12, Hospital Universitario 12 de Octubre, Madrid, Spain; lUniversidad Complutense, Madrid, Spain

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 (0.025–0.035 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.