Case history: Idiopathic Infantile Hypercalcaemia (IIH) classically presents in the first year of life, usually resolves by 1 year of age and is due to mutations in 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1) or, rarely, sodium-phosphate cotransporter-2A (SLC34A1). We report a case of IIH in a Caucasian female, who was born to non-consanguineous parents, with hypercalcaemia, hypercalciuria and associated complications persisting into adulthood. The proband was investigated for delayed developmental milestones and constipation at 7 months old and was found to be hypercalcaemic. Other causes of hypercalcaemia were excluded and she was diagnosed with IIH. Nephrocalcinosis was noted at diagnosis and progressed to a symptomatic renal stone aged 12 years. A DEXA scan following a wrist and heel fracture revealed osteoporosis (SDS −3.2 lumbar spine, -2.15 hip).
Investigations: At diagnosis, biochemistry showed an elevated serum calcium of 3.91 mmol/l (normal range (NR) 2.122.62), normal phosphate of 1.27 mmol/l (NR 0.801.45), elevated magnesium of 1.25 mmol/l (NR 0.751.05), normal 25(OH)D3 of 38.0 μg/ml (NR 750), elevated 1,25(OH)2D3 of 127 pg/ml (NR 2050) and suppressed PTH concentration of <0.7 pmol/l (NR 1.06.1). Her parents were normocalcaemic. In addition, on treatment her plasma calcium concentrations were typically at high-normal limits, and her urinary calcium: creatinine ratios are high and between 0.44 and 1.14 (hypercalciuria defined as >0.20).
Results and treatment: DNA sequence analysis of CYP24A1 revealed compound heterozygous missense mutations comprising Trp134Arg and Leu409Ser, which were inherited from her mother and father, respectively. She was treated with a low calcium and low vitamin D diet that reduced her serum calcium levels, but required pamidronate to normalise her bone mineral density, and had renal stents for nephrolithiasis.
Conclusions and points for discussion: We report a case of IIH in a Caucasian child of non-consanguineous parents, caused by compound heterozygous mutations of CYP24A1. IIH may have a wide spectrum of penetrance and may persist into adulthood and cause renal stone disease and osteoporosis, such that long-term surveillance is recommended. Serum calcium concentrations may be maintained through long-term regulation of dietary calcium and vitamin D. The reported incidence of IIH is ~2 per 100 000 live births in the UK. However, some individuals with IIH may be asymptomatic unless unmasked by supplemental vitamin D treatment, suggesting that the true incidence is higher.
16 - 18 Apr 2018
Society for Endocrinology