ESPE Abstracts

Background: Vitamin D-induced hypercalcemia can result from exogenous vitamin D intoxication, excessive endogenous production or mutations in enzymes involved in vitamin D metabolism.

Case Report: We describe an 8-month-old infant referred to the emergency department with history of failure to thrive and weight loss over the past two months. He was consuming type 2 formula milk supplemented with vitamin D plus vitamin D about 1000 IU/day. Blood tests showed severe hypercalcemia with suppressed PTH and elevated 25-OH-vitamin D level (101 ng/ml – normal value 30-100 ng/ml), along with creatinine levels at the upper limits for age and hypercalciuria without signs of tubulopathy. Considering patient's clinical condition and blood test results, he was admitted for intravenous hyperhydration, low-calcium weaning diet and discontinuation of vitamin D prophylaxis. Due to persistent feeding difficulties, it was necessary to place a nasogastric tube (NGT) to ensure a positive fluid balance and adequate dietary intake. Renal ultrasound revealed marked bilateral nephrocalcinosis with evidence of microlithiasis, for which oral potassium citrate therapy was started. His clinical condition gradually improved, with calcium levels progressively normalizing, although still at the upper limits of normal. Two months after discharge, the NGT was removed due to good weight gain. However, although normal creatinine levels, ultrasound showed nephrocalcinosis damage persisted unchanged Considering the severe nephrocalcinosis, and the slow response to the treatment administered, eleveted FGF23 and borderline 1.25 OH-vitamin D levels were measured. A disorder in vitamin D metabolism was hypothesized. So an NGS panel for tubulopathies was performed, which revealed a compound heterozygosity in the CYP24A1 gene. At the protein level, this resulted in the amino acid deletion p.Glu143del (class 4 – likely pathogenetic), inherited from the father, and the amino acid change p.Leu147Arg (class 3 – VUS), inherited from the mother.

Conclusion: The CYP24A1 enzyme is responsible for converting 1,25-OH-vitamin D into the inactive form 1,24-OH-vitamin D. Loss-of-function mutations in this gene, whether in homozygosity or compound heterozygosity, are associated with hypercalcemia and severe nephrocalcinosis in infants and are a genetic risk factor for serious adverse effects in infants receiving vitamin D supplements for prevention. Although rare, this condition is worth keeping in mind when having an infant with hypercalcemia. The importance of daily vitamin D supplementation in preventing vitamin D deficiency and rickets in infants is well-documented. However, this case underscores the necessity of administering vitamin D carefully to prevent toxicity especially in patients consuming formula milk.