Introduction Activating mutation of the calcium sensing receptor (CaSR), with gain in function in the renal tubule and the parathyroid gland, is associated with hypocalcaemia hypercalciuria. Aggressive treatment to ‘normalise’ serum calcium can lead to progressive hypercalciuria and nephrocalcinosis in the long term. It is important to recognise and distinguish this condition from other well-established aetiologies of primary hypoparathyroidism.
Aims and methods We describe our single centre experience of symptoms, investigations and management of 6 children with activating mutation in CaSR.
Results Four were asymptomatic. One had sensory neural deafness, autism and seizures for several years, with cerebral dysplasia. One had palpitations with flushing episodes, and incidental hypocalcaemia. Initial renal ultrasonography was normal in all. Five were started on alphacalcidol. Shortly after starting treatment, while calcium levels were still low (1.8–2.1), there were sharp rises in the urinary Ca/Cr ratio (up to 1.4) – confirming hypocalcaemic hypercalciuria. Genetic studies confirmed activating mutation of CaSR in all five tested. All children are currently asymptomatic (follow-up 10 months–9 years). Three have now developed nephrocalcinosis.
Conclusions Activating mutation in CaSR is an important cause of primary hypoparathyroidism with hypocalcaemia. Our experience highlights that contrary to literature reports, these children can have profoundly low/unrecordable PTH levels. The key to diagnosis is close monitoring of urinary Ca/Cr ratio – which starts increasing at relatively ‘subnormal’ serum calcium levels. Cautious treatment with alphacalcidol, and close monitoring for ‘optimal’ serum calcium levels to minimise hypercalciuria will help delay the onset of nephrocalcinosis and consequent renal impairment.
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