Variable phenotype of pseudohypoparathyroidism in children

Abstract

Background. Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders associated with tissue insensitivity to parathyroid hormone. PHP is characterized by genetic heterogeneity and variable phenotype. In addition to the hypocalcemic syndrome and resistance to parathyroid hormone, PHP is also characterized by phenotypic features and resistance to other hormones (TSH, LH, FSH, and GHRH), which are known as Albright Hereditary Osteodystrophy (AHO). Until recently, no analysis of large cohorts of patients with PHP has been performed in Russian literature.
 Objective — to examine a large cohort of patients with PHP and assess the clinical features of PHP.
 Material and methods. A group consisting of 32 patients with different variants of course of the disease who had been examined at the Endocrinology Research Center in 2014—2016 was analyzed.
 Results. Features of AHO phenotype in addition to hormonal resistance were identified in 16 (50%) patients; one of them had one feature (brachydactyly) and 15 patients had two and more features of AHO. Besides insensitivity to PTH, TSH resistance was found in 22 (68.75%) patients and one patient had resistance to PTH, TSH and LH/FSH. Hypothyroidism manifested before hypocalcaemia in 4 patients. Obesity was the first complaint in 8 patients; 5 of them had subclinical hypocalcaemia and the remaining 3 patients had an elevated PTH level with the normal level of calcium at the time of first examination. The most typical clinical signs of hypocalcaemia in 23 (72%) patients were seizures. Thirteen of them were misdiagnosed with epilepsy and had been followed by a neurologist for a period ranging between 2 months and 7 years before hypocalcaemia was revealed.
 Conclusions. Pseudohypoparathyroidism is a rare genetic disorder associated with resistance to parathyroid hormone, which can have a lot of other clinical features in addition to the symptoms of PTH resistance. Obesity or hypothyroidism can be the earliest manifestation of PHP preceding hypocalcaemia. Evaluation of serum calcium level is important for all pediatric patients with seizures to timely diagnose hypocalcaemia and avoid misdiagnosing.