CYP24A1 mutations and hypervitaminosis D

Editor – We read with interest the case report entitled ‘Risks of the ‘Sunshine pill’ – a case of hypervitaminosis D’.¹ We wish to congratulate the authors on reporting this remarkable case, and hoped to make some additional contributions.

While noting that hypervitaminosis D is rare and can occur with excessively high doses of supplementation, they omit from their differential diagnoses the possibility of CYP24A1 mutations, a well-described alternate cause of the phenotype described in their patient. Loss of function mutations in CYP24A1 result in reduced action of 1,25-hydroxyvitamin-D₃-24-hydroxylase, which usually inactivates active vitamin D. As well as a neonatal presentation, patients with CYP24A1 mutations can present with adult-onset hypercalcaemia, together with low parathyroid hormone levels and high urinary calcium.^2,3 If this genetic condition is present, even modest vitamin D supplementation can lead to significant hypercalcaemia. Indeed, high levels of active vitamin D metabolites are found in some CYP24A1-deficient individuals even without supplementation.³

We acknowledge that in the case described by Ellis et al supplemental doses were truly high,¹ but the possibility of vitamin D unmasking CYP24A1 mutations should have been considered. The identification of patients with CYP24A1 mutations is important as it allows for tailored lifestyle advice for the patient, screening of at risk family members and opens up the possibility of specific treatments targeting vitamin D production.⁴

In cases of hypercalcaemia, a renal tract ultrasound, looking for nephrocalcinosis, suggestive of a more longstanding kidney disorder, should be performed. Finally we would always advocate taking a detailed family history in such cases, irrespective of the patient’s age, to identify any familial pattern of renal stones, nephrocalcinosis or hypercalcaemia