Endocrine Abstracts (2018) 55 P27 | DOI: 10.1530/endoabs.55.P27

A case of Idiopathic Infantile Hypercalcaemia (IIH) persisting into adulthood, caused by compound heterozygous mutations of 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1)

Victoria Stokes1, Caroline M Gorvin1,2,3, Bahram Jafar-Mohammadi4, Fiona Ryan5 & Rajesh V Thakker1

1Academic Endocrine Unit, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK; 2Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK; 3Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham, UK; 4Department of Clinical Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK; 5Department of Paediatric Endocrinology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.

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) 2.12–2.62), normal phosphate of 1.27 mmol/l (NR 0.80–1.45), elevated magnesium of 1.25 mmol/l (NR 0.75–1.05), normal 25(OH)D3 of 38.0 μg/ml (NR 7–50), elevated 1,25(OH)2D3 of 127 pg/ml (NR 20–50) and suppressed PTH concentration of <0.7 pmol/l (NR 1.0–6.1). 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.

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