Arch Dis Child 2012;97:A122 doi:10.1136/archdischild-2012-301885.291
British Association of General Paediatrics/British Society for Paediatric Endocrinology & Diabetes
D Finn 1, S How Yaw 1, V Mathew 1, K Prescott 2, S Gupta 1
1 Department of Paediatrics, Hull Royal Infirmary, Hull, UK
2 Department of Clinical Genetics, Chapel Allerton Hospital, Leeds, UK
Aim Activating mutations of CaSR gene have been shown to cause hypercalciuric hypocalcaemia1. The CaSR plays a key role in maintaining calcium homeostasis by regulating parathyroid hormone (PTH) and renal calcium reabsorption. Activating mutation of CaSR causes increased sensitivity to Ca++ and hence down regulation of PTH secretion.
Method This is a case series where we report a pedigree with clinical picture consistent with familial autosomal dominant hypoparathyroidism. The proband, an 18-month-old girl was found to have incidental hypocalcaemia. We identified 4 other affected individuals in the family, including the father of the proband and his twin brother. All affected individuals had mild hypocalcaemia, low normal serum parathyroid levels and borderline high phosphate levels.
Treatment with vitamin D and oral calcium did not improve their serum calcium levels. The father of proband has shown evidence of hypercalciuria and has recently been treated for urolithiasis. Mutation analysis identified a novel activating mutation of the CaSR gene c.407C>T (p.Pro136Leu) in all 3 family members who were tested.
Conclusion Activating mutation of the CaSR inhibits PTH secretion and renal calcium reabsorption despite hypocalcaemia. Treatment with vitamin D and calcium can increase hypercalciuria leading to nephrocalcinosis and renal impairment1,2. Asymptomatic individuals should not be overtreated in an attempt to normalise serum calcium.
- - - - - - - - - - -