Background: Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder due to inactivating mutations in the calcium sensing receptor (CASR). FHH is generally benign with asymptomatic hypercalcaemia, low urinary calcium excretion and normal or mildly elevated PTH.
Objective and hypotheses: We report a novel mutation in CASR in a family with three generations affected with hypercalcaemia.
Method: A 15 -month-old boy was found to have asymptomatic hypercalcaemia when admitted for elective tonsillectomy. Further investigations revealed normal PTH, phosphate and vitamin D levels. Urine calcium/creatinine (Ca/Cr) clearance ratio was low. A younger brother born a few months later also had asymptomatic hypercalcaemia and hypocalciuria. Investigation of family members showed raised calcium in the index cases mother and maternal grandfather, but not in his father or older brother.
Results: CASR sequencing of the family has revealed a previously undescribed T to C nucleotide substitution in exon 4 of CASR (c.1342T>C (p.Ser448Pro)). The index case, younger brother, mother and grandfather are all heterozygous for this unclassified variant (Table 1).
|Adj. S. calcium (2.22.79 mmol/l)||PTH (1.16.9 mmol/l)||S. phosphate (1.362.26 mmol/l)||Ca/Cr clearance ratio||Vitamin D (nmol/l)|
Conclusion: We describe a novel mutation in the CASR gene in three generations of the same family with biochemical diagnosis of FHH.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology