Sota Iwafuchi, Nao Uchida, Naoya Saijo, Chisumi Sogi, Miki Kamimura, Jun Takayama, Gen Tamiya, Atsuo Kikuchi, Junko Kanno
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 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 variants. Herein, we describe a case of IIH triggered by vitamin D-fortified milk consumption in a 9-mo-old male patient carrying a 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)D (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 (NM_000782.5) locus. Unexplained hypercalcemia in infants should raise suspicions of abnormal vitamin D metabolism and locus genotypic analysis can be informative in this regard.
