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Endocrine Abstracts (2017) 49 EP305 | DOI: 10.1530/endoabs.49.EP305

ECE2017 Eposter Presentations: Calcium and Bone Calcium & Vitamin D metabolism (65 abstracts)

Pseudohypoparathyroidism (PHP) and GNAS gene mutations – clinical spectrum from PHP type 1a to pseudopseudohypoparathyroidism

Ana Saavedra 1, , Elisabete Rodrigues 1, , Filipe Cunha 1, , Miguel Leão 3 & Davide Carvalho 1,

1Department of Endocrinology, Diabetes and Metabolism of Centro Hospitalar de São João, Porto, Portugal; 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Department of Genetics of Centro Hospitalar de São João, Porto, Portugal.

Introduction: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders that have in common end-organ unresponsiveness to parathyroid hormone (PTH). The most frequent form, PHP type 1, results from different genetic/epigenetic changes in the GNAS gene.

Case 1: Woman, 25 years-old, sent to Endocrinology from Genetics consultation after her daughter had been diagnosed with PHP type 1a (heterozygous pathogenic variant at exon 13 of GNAS gene c.1174G>A (p.e392K)). Our patient and her father present some clinical manifestations as observed in the child, suggestive of Albright Hereditary Osteodystrophy (AHO), and both present the same mutation as encountered in index case. We tested phosphocalcic metabolism of our patient and she presented normal serum calcium/phosphorus levels as well PTH levels. Other pituitary hormones were evaluated, with normal results except elevated TSH (18.72 μUI/ml) in context of primary autoimmune hypothyroidism. Patient started treatment with levothyroxine.

Case 2: Male, 31 years-old (case 1 brother). He was sent to Endocrinology in December 2015 for lymphocytic thyroiditis evaluation. During the physical examination, it was recognized a phenotype suggestive of AHO, as was found in his relatives (round facies, brachydactyly and subcutaneous calcifications). Patient’s lab tests showed normal serum calcium/phosphorus levels and high PTH in the context of vitamin D deficiency. Other pituitary hormones levels were in normal range. Patient performed genetic test - results ongoing.

Conclusion: Different pathological entities may result from mutations in the GNAS gene. PHP type 1a is characterized by the presence of AHO and PTH resistance. However, AHO manifestations may occur in patients without PTH resistance (pseudopseudohypoparathyroidism), as in the two cases presented. This occurs when the mutation is paternally transmitted. These cases somehow demonstrate de complexity of GNAS gene mutations, which merited recently a new classification. It is also highlighted that although pseudopseudohypoparathyroidism needs no treatment, genetic counselling should also be recommended.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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