ESPE Abstracts

Background: Pseudohypoparathyroidism is a rare congenital disorder presenting with variable symptoms and features. Since 2016 a new international nomenclature subclassifies the different forms of pseudohypoparathyreoidism as inactivating PTH/PTHrP signalling disorders (iPPSD). Pseudohypoparathyreoidism 1A (iPPSD2) and 1B (iPPSD3) are mainly characterized by resistance of parathyroid hormone (PTH) with high serum PTH levels and thyrotropin (TSH) resistance. In both forms, iPPSD2 and 3, cerebral calcifications can be found. As these patients may develop hypogonadotropic hypogonadism and growth hormone deficiency, puberty and height velocity of patients should be closely monitored.

Case presentation: We present a four-year-old boy, hospitalised with the suspected diagnosis of epilepsy. He showed clinical features reminding of absence seizures and musculoskeletal convulsions. As ionized calcium concentration was very low at several occasions (0.84 mmol/l, range: 1.0-1.9 mmol/L) hypocalcemia was found to be the cause of the recurrent absences. The patient presented with an excessive high level of PTH (515 pg/ml, range: 15-65 pg/mL)) as well as with high serum phosphate levels (2.91 mmol/l, range: 1.05-1.8 mmol/L). We started to substitute calcium (2 g/day) and alfacalcidol (50 ng/kg per day). In order to avoid hypercalciuria and consecutive nephrocalcinosis we closely monitored serum calcium levels as well as urine levels of calcium and phosphate. Due to macrosomia and normal cognitive development, we suspected pseudohypoparathyreoidism 1B. On genetic investigation, a hypermethylation of NESP55 and a hypomethylation of NESPAS/GNASXL in the GNAS locus were found. This pattern has already been described and associated with the diagnosis of pseudohypoparathyreoidism 1B. The assessment of the DNA of patient`s parents with regard to a potential UPD20 is underway. In addition, we plan a MRI to reveal cerebral calcifications.

Conclusion: Hypocalcemia may cause neurological symptoms such as seizures. A thorough work-up of the calcium-phosphate metabolism including genetic analysis is necessary to define the etiology of the disorder such as PHP1B (iPPSD3) in the presented case.