Aspectos clínicos en dos casos de seudohipoparatiroidismo ( Ia y Ib) y estudio molecular del locus GNAS / Clinical features of two cases of pseudohypoparathyroidism ( I a and I b) and molecular analysis of GNAS

RESUMEN

El seudohipoparatiroidismo (PHP) es una entidad rara, caracterizada por resistencia tisular a la hormona paratiroidea (PTH). Los 2 subtipos principales, PHP-Ia y PHP-Ib, son causados por alteraciones en el gen GNAS (20q13.3), que codifica para la proteína Gsα, esencial para la acción de la PTH y otras hormonas. El PHP-Ia se asocia a diversas alteraciones hormonales, osteodistrofia hereditaria de Albright (AHO) y actividad reducida de Gsα. Está causado por mutaciones inactivantes del gen GNAS. El PHP-Ib presenta resistencia aislada a la PTH, sin AHO y con actividad Gsα normal o levemente baja. Se asocia a defectos en la impronta de GNAS. Se presentan 2 casos con PHP-Ia y PHP-Ib, ahondando en su clínica y en el diagnóstico diferencial frente a afecciones similares (AU)

ABSTRACT

Pseudohypoparathyroidism (PHP) is a rare disorder, characterized by a tissue resistance to parathyroid hormone (PTH). The two main subtypes of PHP, PHPIa and PHPIb, are caused by alterations in the GNAS locus (20q13.3), which encodes the Gs protein, essential for the action of PTH and other hormones. PHP-Ia is associated with several hormone resistances, Albright hereditary osteodystrophy (AHO), and reduced Gsα activity. It is caused by inactivating mutations in the GNAS gene. PHPIb presents with isolated resistance to PTH, without AHO and with normal to low Gsα activity. It is related to imprinting defects in GNAS. Two unrelated cases of PHP-Ia and PHP-Ib are presented here, focusing on their clinical aspects and in the differential diagnosis with similar pathologies (AU)