ESPE Abstracts

Background: The calcium-sensing receptor (CASR) is Class C G protein-coupled receptor (GPCR). CASR is responsible of calcium set point and it is expressed in several tissues: parathyroid, C-Cells, and kidney cells. CASR activating mutations are responsible of autosomal dominant hypocalcaemia 1 (ADH1; OMIM # 601198) and more than 100 different mutations have been described. ADH1 is not always associated with hypercalciuria. Nagase et al. described for the first time CASR Ser820Phe mutation in a Japanese family.

Case description: A six-months-old female infant was referred to our clinic because of persistent mild hypocalcaemia since the first day of life. Hypocalcaemia was associated with failure to thrive and hypoglycaemia, the patient’s mother presented gestational diabetes. Newborn was observed in neonatal sub intensive care and an abdominal echography was normal. Hypocalcaemia has been reconfirmed. She was on therapy with supplementation in cholecalciferol. Hyperphosphatemia (mean value 7.6 mg/dL) and hypomagnesemia (mean value 1.9 mg/dL) have been documented associated with normal/low parathyroid hormone levels (mean values <10 pg/mL) during follow up. The urinary calcium excretion was out of normal range. Calcific formations have been described in midollary region of both kidneys since her eight months of life. Because of these and hypercalciuria, therapy is cautiously modulated with low dose of cholecalciferol and Ca2 oral supplementation. Calcium levels are maintained to low limit. Genetic testing revealed the Ser820Phe mutation in single allele localized in exon 7 that is considered pathogenetic: the patient was diagnosed with Autosomal Dominat Hypocalcemia type 1 associated with hypercalciuria. The family history from mother’s side was positive for epilepsy.

Conclusion: In contrast to our case, Nagase et al. report none kidney calcific formation and a normal urinary calcium excretion in their patients. In García-Castaño et al paper, Ser820Phe mutation is described as cause of only hypoparathyroidism. Currently, no association between genotype-phenotype is reported. According to literature, hypercalciuria was detected only in 34% of patients.² In our case, calcific formation was present since infant age. A recent paper has faced the specific role of CASR in kidney district. Furthermore information and clinical reports are necessary to fully understand the pathologic meaning of mutations and the specific meaning of CASR’s mutations in different tissues.