Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos

Abstract

Pseudohypoparathyroidism: report of two cases of late presentation Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyper-phosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth`s Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting , they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroi-dism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism. (Rev Med Chile 2018; 146: 116-121) Introducción E l término pseudohipoparatiroidismo (PHP) comprende un grupo de trastornos gené-ticos infrecuentes, que tienen en común la resistencia a la acción de la paratohormona (PTH) en el túbulo renal proximal, afectando allí la excreción de fosfato y la síntesis de calcitriol, metabolito más activo de la vitamina D. El PHP se manifiesta bioquímicamente por hipocalcemia, hiperfosfemia y PTH elevada sin evidencia de falla renal y/o hipomagnesemia 1. Algunas variantes de esta patología pueden presentar un fenotipo espe-cífico caracterizado por talla baja, facies redonda, cuello corto, obesidad, braquidactilia, osificación heterotópica y discapacidad intelectual variable, conocido como osteodistrofia hereditaria de Al-bright (OHA) 2. En otros casos de PHP, se observa solo fenotipo de OHA, pero sin manifestaciones bioquímicas de resistencia a PTH, tales pacientes se denominan como pseudopseudohipopatiroidis-mo (PPHP) 3. La prevalencia estimada del PHP es de 0,79 por 100.000 habitantes 2. Este conjunto de patologías se producen por mutaciones del gen GNAS, el cual codifica para la subunidad alfa de la proteína G (Gsa). La