Endocrine Abstracts

Idiopathic infantile hypercalcaemia (IHH) is an autosomal recessive disorder typically presenting in the first few months of life with failure to thrive, vomiting, dehydration, and nephrocalcinosis with hypercalcaemia and low or undetectable parathyroid hormone (PTH) concentrations. IHH is caused by loss-of-function mutations of the cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene that encodes the 514 amino acid protein 1,25-dihydroxyvitamin D₃ 24-hydroxylase which converts the active 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) to the inactive metabolite 1,24,25(OH)₃D₃, thereby resulting in elevated 1,25(OH)₂D₃ concentrations and hypercalcaemia. We report a case of IHH in a Caucasian female born to a non-consanguineous family. The proband was born by elective Caesarean section at 38 weeks gestation for placenta praevia and had poor feeding, lethargy, weight loss, jaundice and a baseline bradycardia shortly after birth. At 7 months old she was investigated for delayed developmental milestones and constipation and was found to have an elevated serum calcium of 3.91 mmol/l (normal range 2.12–2.62), normal phosphate of 1.27 mmol/l (normal range 0.80–1.45), elevated magnesium of 1.25 mmol/l (normal range 0.75–1.05), normal 25(OH)D₃ of 38.0 μg/ml (normal range 7–50), elevated 1,25(OH)₂D₃ of 127 pg/ml (normal range 20–50) and suppressed PTH concentration of <0.7 pmol/l (normal range 1.0–6.1). Other causes of hypercalcaemia including William’s syndrome were excluded and she was diagnosed with IHH. She was placed on a strict low calcium and low vitamin D diet and this resulted in marked reductions in serum calcium concentrations (range =2.54–2.66 mmol/l) and a clinical improvement. DNA sequence analysis of the 12 coding exons and intron-exon boundaries of CYP24A1, using leukocyte DNA, revealed her to be homozygous for a transition of a T to C at position 1620 within exon 9, that predicted a missense Leu409Ser mutation that has been reported to severely impair CYP24A1 function in vitro and cause IHH.