Background: Neonatal severe hyperparathyroidism (NSHPT) has been associated with inactivating mutations of the calcium-sensing receptor (CASR) gene. Impaired inhibition of PTH secretion by extracellular ionized calcium and decreased urinary excretion of calcium leads to severe hypercalcemia in the first days of life. Calcium responsiveness of the CaSR is amplified by type 2 calcimimetic agents like cinacalcet, which has been able to normalize PTH and calcium levels in cases of NSHP and postpone parathyroidectomy.
Case report: A full-term female newborn presented with severe respiratory distress due to thoracic and pulmonary hypoplasia at birth and hypotonia and failure to thrive in the following weeks. On the sixth day of life the serum calcium level was elevated to 3.27 mmol/l. Further evaluation showed hyperparathyroidism in the presence of low urinary calcium excretion. Sequence analysis of the CASR gene revealed a de novo heterozygous mutation in exon 4 (c.554G>A; p.R185Q). Forced diuresis and a single dose of pamidronate did not improve hypercalcemia. While cinacalcet therapy normalized PTH secretion and increased urinary excretion of calcium, serum calcium levels remained elevated above 3.27 mmol/l and the patient developed progressive nephrocalcinosis.
Discussion: The mutation above has been associated with NSHPT that has successfully been treated with cinacalcet experimentally. A dosage has not been established for this indication and long-term side effects are unknown. In the presence of normal PTH levels and increased urinary calcium excretion other gene mutations have been discussed to additionally impair calcium sensing in patients who do not reach eucalcemia.
Conclusion: Cinacalcet offers an option to treat NSHPT resulting from inactivating mutations in the CASR gene. Laboratory parameters and ultrasound of the kidneys have to be closely monitored in order to prove the effect of the therapy and avoid side effects. Additional factors affecting hypercalcemia and calcium sensing should be considered.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology