CYP24A1 mutations and hypervitaminosis D
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* Jamie Willows
* John A Sayer

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

*   © Royal College of Physicians 2019. All rights reserved.

## References

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