Endocrine Abstracts

Background: The 24-hydroxylase enzyme is responsible for the degradation of 1,25-dihydroxyvitamin D₃. Loss of function mutations of the gene encoding 24-hydroxylase, CYP24A1, may cause hypercalcaemia, nephrolithiasis and nephrocalcinosis, and are responsible for some cases of idiopathic hypercalcaemia of infancy.

Case: The index case presented with faltering growth at 4 months old. She was hypercalcaemic with serum calcium 2.79 mmol/l (normal range 2.15–2.60 mmol/l), ionised calcium 1.61 mmol/l (normal range 1.1–1.35 mmol/l), intact parathyroid hormone 1.1 pmol/l (normal range 0.5–6.4 pmol/l) and phosphate 1.58 mmol/l (normal range 0.78–1.53 mmol/l). Her initial 25-hydroxyvitamin D was 155 nmol/l (normal range 72–374 nmol/l). There was hypercalciuria, bilateral medullary nephrocalcinosis and unexplained aminoaciduria, without a history of dietary supplementation. Subsequently, her growth was normal and her secondary dentition had poor enamel and increased sensitivity. Bendroflumethiazide was instituted for persistent hypercalciuria. Screening of her younger, asymptomatic sister at 8 weeks of life confirmed hypercalcaemia, hypercalciuria and nephrocalcinosis. The siblings were treated with low-calcium and low-vitamin D diets and the calcium returned to normal. Calcium was gradually re-introduced and normal feeds were re-commenced from between 12 and 18 months of age. Hypercalciuria persisted, however the hypercalcaemia resolved, the nephrocalcinosis did not progress and neither sibling had fractures. The siblings were found to have loss of function mutations of CYP24A1 at R396W and L409S. Their father has short stature and mild hypercalciuria but no nephrocalcinosis and has not yet had mutation testing.

Conclusions: We highlight that CYP24A1 mutations are a cause of transient hypercalcaemia in infancy. As hypercalcaemia resolves spontaneously, CYP24A1 mutation screening should be considered in older children without hypercalcaemia but with nephrocalcinosis and hypercalciuria, particularly if other family members are affected.