ESPE Abstracts (2016) 86 P-P1-696

Variable Phenotype and Genetic Findings in a Cohort of Patients with Pseudohypoparathyroidism

Nadezhda Makazana, Elizaveta Orlovaa,b, Maria Karevaa, Natalia Kalinchenkoa, Elena Tozliyanc, Ivan Dedova & Valentina Peterkovaa

aEndocrinology Research Centre, Moscow, Russia; bI.M.Sechenov First Moscow State Medical University, Moscow, Russia; cResearch & Clinical Institute for Pediatrics n.a. acad. Y.E.Veltishev, Moscow, Russia

Background: Pseudohypoparathyroidism is a group of rare disorders characterized by tissue insensitivity to PTH and Albright hereditary osteodystrophy (AHO) due to inactivating mutations or epigenetic defects of the GNAS.

Objective and hypotheses: Clinical features and molecular characteristics of patients with PHP have been examined.

Method: We included 28 patients from 26 families with PHP1a and 1b. GNAS mutation analysis was performed in patients with AHO signs. Clinical data were analyzed.

Results: The first clinical signs in 20 patients (71.4%) were seizures. 11 of them were misdiagnosed with epilepsy and had been receiving anticonvulsants for 2 month – 7 years before hypocalcemia was revealed. Obesity was the first complain in seven patients, one of them had hypothyroidism manifested before hypocalcemia. One patient had only growth and mental retardation and was examined because of sister’s disease. 19 patients had TSH resistance and one had GnRH resistance. AHO features were observed in 13 patients. The most common feature was brachymatecarpia (13 patients), subcutaneous calcifications was seen in eight patients, obesity was seen in seven patients, moon face had five patients, short stature had five patients, mental retardation were observed in six patients. 17 patients had complications of hypocalcemia: Fahr’s Syndrome (60.7%), 5 had cataracts (17.8%). Maternally-inherited GNAS mutations were identified in two patients (siblings), de novo GNAS mutations were identified in five patients with PHP1a.

Conclusion: Obesity or hypothyroidism can precede hypocalcaemia in PHP. Evaluation of serum Ca is important for all patients with seizures to avoid misdiagnosing. Absence of GNAS mutation in patients with AHO indicates overlap between PHPIa and PHPIb. Further investigations including MS-MLPA assay are planned to explore potential phenotype-genotype correlations in PTH.

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