Idiopathic infantile hypercalcemia with a CYP24A1 variant triggered by vitamin D supplementation in fortified milk: a case report

Abstract

Idiopathic infantile hypercalcemia (IIH) is characterized by hypercalcemia, nephrocalcinosis, vomiting, dehydration, and failure to thrive. It is caused by the presence of biallelic loss-of-function variants in the CYP24A1 locus. Although hypercalcemia has been linked to the consumption of vitamin D-fortified milk, no reports have documented its role in triggering IIH in patients with CYP24A1 variants. Herein, we describe a case of IIH triggered by vitamin D-fortified milk consumption in a 9-mo-old male patient carrying a CYP24A1 variant. After BCG vaccination, the patient developed a facial rash, became anorexic, appeared to be in a bad mood, and began consuming vitamin D-fortified milk instead of baby food. Blood tests showed a marked hypercalcemia (18.5 mg/dL), high 1,25-(OH)₂D (98.7 pg/dL) levels, and low parathyroid hormone (PTH) (< 4.0 pg/dL) and PTHrP (< 1.0 pg/dL) levels. The calcium levels were successfully normalized after treatment with saline loading, furosemide, pamidronate, and a low-calcium milk diet. After discharge, blood calcium levels remained normal with no recurrence of symptomatic hypercalcemia, but circulating PTH levels were persistently suppressed. Renal ultrasonography at 8 yr of age revealed high medullary echogenicity and diffuse echogenic foci in both kidneys. Trio-based whole-genome sequencing identified the following biallelic pathogenic variants c.[464G>A];[1324C>T], p.[Trp155Ter];[Gln442Ter], in the CYP24A1 (NM_000782.5) locus. Unexplained hypercalcemia in infants should raise suspicions of abnormal vitamin D metabolism and CYP24A1 locus genotypic analysis can be informative in this regard.