ESPE Abstracts

Introduction: Idiopathic infantile hypercalcemia (IIH) is characterized by hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. Biallelic loss-of-function variants in the CYP24A1 —which encodes the vitamin D-24-hydroxylase that regulates 1,25-(OH)2D catabolism—have been associated with IIH. Cases of IIH with CYP24A1 variants reportedly have several complications—including nephrocalcinosis, cardiovascular disease, and intellectual disability. Therefore, accumulating case reports of IIH with CYP24A1 variants potentially contribute to early diagnosis and treatment. Herein, we report a case of IIH possibly triggered by fortified milk with the CYP24A1 variant.

Case report: A 9-month-old boy—the third child of healthy, nonconsanguineous Japanese parents—was vaccinated with Bacillus Calmette–Guérin (BCG) at 7 months of age. After 3 weeks of vaccination, rashes appearing on his right cheek and fever occurred. Consequently, he stopped eating baby foods and instead drank fortified milk. On admission, blood tests showed remarkable hypercalcemia (18.0 mg/dL), high 1,25-(OH)2D levels, and low parathyroid hormone (PTH) and PRTH-related protein (PTHrP) levels. After being introduced to milk with a low calcium content, his calcium levels normalized. However, FECa was >1%, PTH and PTHrP levels remained low, and active vitamin D levels remained high. No findings indicated sarcoidosis or malignant lymphoma. During hospitalization, fever, lymphadenopathy in the left neck, and BCG vaccination site swelling—a symptom of papulonecrotic tuberculid as a BCG vaccination side effect—occurred twice. However, all symptoms eventually disappeared without any medication. Postdischarge, the serum calcium level usually remained normal; however, whole PTH was persistently suppressed. When the patient was 8 years old, renal ultrasound showed high medullary brightness in both kidneys and scattered twinkling, indicating calcium metabolism abnormality; thus, trio-based whole-genome sequencing was conducted, revealing biallelic pathogenic variants in CYP24A1. One of these variants was p.Trp155Ter—a stop-gain variant of c.464G>A and a previously reported causative variant of hypercalcemia. Another variant was a stop-gain variant of c.1324C>T called pGln442Ter, which was not reported previously but could be pathogenic.

Conclusions: Early diagnosis of IIH is crucial for the long-term prognosis of infants. Considering the possibility of abnormal vitamin D metabolism and analyzing CYP24A1 may be useful in infants with unexplained hypercalcemia.