Pseudohypoparathyroidism and its various phenotypes: three sisters with three different clinical presentations

Authors

  • Fabio Sippelli Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina
  • Chiara Ferraloro Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina
  • Giulia Visalli Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina
  • Giulia Cafarella Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina
  • Domenico Corica Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina
  • Malgorzata Wasniewska Department of Human Pathology in Adulthood and Childhood, “G. Barresi”, University of Messina

DOI:

https://doi.org/10.13129/1828-6550/APMB.109.2.2021.CCS6

Keywords:

pseudohypoparathyroidism, Albright osteodystrophy, PTH resistance, Gs-alpha protein

Abstract

Pseudohypoparathyroidism (PHP) is a heterogeneous group of hereditary disorders characterized by clinical and biological characteristics of resistance to parathyroid hormone (PTH) caused by impaired hormonal signalling via receptors that are coupled, through the α- subunit of the stimulatory G protein (Gsα). In some cases, resistance to other hormones (such as TSH, gonadotropins, GHRH and calcitonin) that have receptors coupled via Gsα is observed. A subset of patients with PHP are characterized by the variable expression of a collection of physical features, termed Albright hereditary osteodystrophy (AHO), which includes brachydactyly, rounded face, short stature, central obesity, subcutaneous ossifications, and variable degrees of mental retardation. These patients face a wide range of problems from early childhood to adulthood, which include potentially severe alterations in mineral metabolism, which could be associated with seizures; other endocrine deficiencies due to hormone resistance that lead to hypothyroidism, hypogonadism and GH deficiency; growth impairment independently of hormonal status; ectopic ossifications with potential severe limitation of mobility; skeletal issues and cognitive and psychomotor impairment.

Here we report three sisters affected by pseudohypoparathyroidism but with remarkably differences from each other in terms of phenotypic and clinical-auxological characteristics, a demonstration of how this disease is characterized by a very heterogeneous phenotype, even among patients carrying the same genetic alteration.

References

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Published

2021-08-27

Issue

Vol. 109 No. 2 (2021)

Section

CLINICAL CASE SEMINAR

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