Adult height and long-term outcomes after rhIGF-1 therapy in two patients with PAPP-A2 deficiency

PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse ef...

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Detalles Bibliográficos
Autores: Martín-Rivada, Álvaro, Barrios, Vicente, Martínez Díaz-Guerra, Guillermo, Pozo Román, Jesús, Martos Moreno, Gabriel Ángel, Argente Oliver, Jesús
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/700703
Acceso en línea:http://hdl.handle.net/10486/700703
https://dx.doi.org/10.1016/j.ghir.2021.101419
Access Level:acceso abierto
Palabra clave:Bone density
Free IGF-1
GH/IGF-1
Growth
Total IGF-1
PAPP-A2
rhIGF-1
Medicina
Descripción
Sumario:PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse effects, but data regarding the long-term efficacy and safety of rhIGF-1 administration in this entity has not yet been reported. Two Spanish siblings with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) were treated with rhIGF-1 twice daily for six years. Growth velocity continued to increase and both patients achieved their target height. Free IGF-1 concentrations increased notably after rhIGF-1 administration, with serum IGFBP-3, IGFBP-5 and ALS levels also being higher during treatment. BMD was progressively normalized and an increase in lean mass was also noted during treatment. No episodes of hypoglycemia or any other adverse effects were documented. An increase in the growth of kidney and spleen length was observed in one of the patients