ESPE Abstracts (2015) 84 P-3-644

Clinical and Molecular Characterisation of Patients with Pseudohypoparathyroidism

Eungu Kanga, Yoon-Myung Kima, Ja Hyang Choa, Gu-Hwan Kimb, Jin-Ho Choia & Han-Wook Yooa,b


aDepartment of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul, Republic of Korea; bMedical Genetics Center, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul, Republic of Korea


Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphataemia and Albright hereditary osteodystrophy (AHO), resulting from abnormalities of GNAS.

Objective and hypotheses: This study investigated clinical features, outcomes, molecular characteristics of patients with PHP and pseudopseudohypoparathyroidism (PPHP).

Method: Thirty one patients (15 males and 16 females) from 26 families with PHP1a, PHP1b, and PPHP were enrolled. GNAS mutation analysis and methylation-specific multiplex ligation-dependent probe amplification was performed to assess genetic and epigenetic alterations. Clinical data including presenting symptoms, outcomes, and endocrinologic findings were analysed retrospectively.

Results: The age at diagnosis was 7.04±5.2 years. Maternally-inherited GNAS mutations were identified in 14 patients of PHP1a, and paternally-transmitted mutations in 3 patients with PPHP. Twelve PHP1b patients harboured paternal uniparental disomy. Two patients of PHP1b demonstrated loss of methylation on exon 1A of GNAS by heterozygote deletion of nearby STX16. Serum total calcium and phosphorus levels at diagnosis were 7.24±2.04 mg/dl and 7.2±2.11 mg/dl respectively. The parathyroid hormone (PTH) and 25-hydroxyvitamin D3 levels were 367.70±240 pg/ml and 28.54±16.66 ng/ml respectively. The age at the start of calcium supplementation was 9.2±5.6 years. Five patients (three PHP1a and two PHP1b) manifested subclinical hypothyroidism earlier than the onset of hypocalcaemia, requiring L-thyroxine therapy at age 2.0±1.8 years. Two PHP1b patients were initially diagnosed with transient congenital hypothyroidism, and presented with hypocalcaemic seizure at age 10 and 17 years respectively.

Conclusion: This study suggests that the mode of clinical presentation of patients with PHP is bimodal: hypothyroidism in the earlier age and hypocalcaemia later in childhood. Long-term follow-up for growth patterns, pubertal progression, obesity, thyroid functions, serum PTH, calcium, and phosphorus levels should be assessed on a regular basis in order to introduce appropriate treatment in these patients.

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