[INTRODUCTION - Familial hypocalciuric hypercalcemia and neonatal severe primary hyperparathyroidism are caused by inactivating mutations of the calcium-sensing receptor (CaSR) gene. We report the case of a now 9.5 years old boy who presented with the clinical syndrome of neonatal severe hyperparathyroidism. PATIENT AND METHODS - At the age of 2 days the patient developed respiratory distress. Clinical studies revealed increased serum calcium (3.1 mmol/l), non-suppressed serum parathyroid hormone level (48.3 pg/ml) and severe undermineralization of bones, as well as periosteal calcification in the distal part of both femurs suggesting fractures during the intrauterine life. Parathyreoidectomy was not performed.At the age of 6 years normal mental and physical development, persisting hypercalcemia without clinical symptoms, normal skeletal morphology, absence of new bone fractures, and absence of renal stones or nephrocalcinosis were documented, and the patient has remained completely symptom-free until his present age of 9.5 years. Sequence analysis of the entire coding region (exons 2-7) of the CaSR gene in peripheral leukocyte DNA revealed a heterozygous mutation at codon 551 (AGG→AAG) predicting a change of arginine to lysine (R551K). In addition, a known heterozygous polymorphism at codon 986 (GCC→TCC) was found in the proband and in his father. CONCLUSION - Our patient seems to represent the fourth reported case of neonatal severe primary hyperparathyroidism with a heterozygous de novo mutation of the CaSR gene. In addition, this case provides new evidence that with time the disease of neonatal severe hyperparathyroidism may spontaneously turn into a symptomless, benign condition resembling familial hypocalciuric hypercalcemia.]

[INTRODUCTION - Parathyroid hormone (PTH) excretion is increased both in primary hyperparathyroidism (pHPT) and in pseudohypoparathyroidism type Ia (PHP Ia). Pseudo-pseudohypoparathyroidism (P-PHP) is considered to be the normocalcemic form of pseudohypoparathyroidism type Ia. Our aim was to assess bone mineral content and bone quality as well as to determine whether these parameters are related to PTH levels in the above mentioned disorders. PATIENTS AND METHOD - 10 patients with pseudopseudohypoparathyroidism (P-PHP, age: 41.6 ±5.4 ys) were compared to 10 patients with primary hyperparathyroidism (pHPT) and to 10 healthy subjects, matched for age and gender. Moreover, nine patients with pseudohypoparathyroidism type Ia (PHP, age: 34.2 ±5.43 ys) were compared to nine age- and gender-matched patients with primary hyperparathyroidism and to nine healthy controls, respectively.The occurrence of previous bone fractures was recorded and bone mass was measured (by dual photon absorptiometry on the axial bones and by single photon absorptiometry on the forearm). Quantitative ultrasound (QUS) examination was performed both on the calcaneus by broadband ultrasound attenuation (BUA, dB/MHz) and speed of sound (SOS, m/s) measurements and on the proximal phalanges by amplitude-dependent speed of sound (AdSOS, m/s) measurements. In addition, some laboratory parameters of calcium metabolism were tested. RESULTS - No difference was found between PHP Ia and pHPT in bone mass.The lowest value was observed at the radius. Among the QUS parameters, pathologically low AdSOS was found at the phalanges in PHP Ia and it was lower than in pHPT patients, whereas at the calcaneus BUA showed a similar tendency. Bone mass did not significantly differ between P-PHP and healthy controls, it was decreased, however, at the forearm in the patients. Pathological AdSOS was found in P-PHP, which was lower than in pHPT. SOS at the calcaneus was lower in P-PHP than in pHPT, though it was not considered pathological. Laboratory results were typical for the diseases and the radiological examinations confirmed the diagnosis. Bone fractures occurred in three and two patients with PHP Ia and P-PHP, respectively, while no fractures were recorded in the pHPT and healthy groups. CONCLUSION - Bone loss among patients with PHP Ia is considered to be the impact of PTH excess on bone tissue.The deterioration of bone quality and architecture may play a role in the development of bone fractures.]

[The extracellular calcium-sensing receptor (CaSR) was recognized and cloned a decade ago. It is a G-proteincoupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. Diseases known as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism and autosomal dominant hypocalcemia are the consequences of naturally occurring mutations of the CaSR. However, the spectrum of the CaSR diseases became more complex with the recognition of both hypo- and hypercalcemic states caused by anti-CaSR autoantibodies. Activating anti-CaSR autoantibodies have been implicated in the pathogenesis of isolated idiopathic hypoparathyroidism and of hypoparathyroidism associated with autoimmune polyglandular syndromes. Inactivating CaSR autoantibodies may cause fluctuating hypercalcemic disorder that resembles primary hyperparathyroidism. The CaSR recently became one of the most intensively investigated target of potential new drugs. Cinacalcet has been approved for the treatment of secondary hyperparathyroidism associated with chronic renal insufficiency and for the management of inoperable or metastatic parathyroid carcinoma.The CaSR may be one of the main molecular target of strontium ranelate, wich is a new antiosteoporotic compound.]