O-12 A rare cause of parathyroid hormone independent hypercalcemia: 1,25-(OH)2D-24 Hydroxylase (CYP24A1) deficiency

Abstract

Abstract Background Common causes of parathyroid hormon (PTH)-independent hypercalcemia in adulthood are malignancy, granulomatous diseases, and endocrinopathies. Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, can also be a rare cause of supressed intact PTH levels, usually associated with, nephrolithiasis and nephrocalcinosis. This disease, defined as idiopathic infantile hypercalcemia, classically presents with hypercalcemia in infants. However, some individuals have also been reported with late-onset clinical manifestation or late diagnosis in adulthood. Clinical Case A 59-year-old male patient with a known diagnosis of type 2 diabetes mellitus for 30 years. He had a history of recurrent kidney stones since 2006. His blood and urine tests revealed elevated creatinine level, hypercalcemia with normal phosphorus levels, normal 25-hydroxycholecalciferol levels, suppressed intact PTH level and normal 24-hour urinary calcium level (Table 1). Urinary ultrasonography was consisted with medullary nephrocalcinosis and chronic kidney disease. PTH-independent causes of hypercalcemia were investigated. Malignancies, granulomatous diseases and endocrinopathies were ruled out. The 1,25-dihydroxycholecalciferol level was within the normal range. Parathormone related peptide level was determined as 1.60 pmol/L (normal value <4.2). Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. Thereupon, genetic screening started on the siblings of the patient which not been finalized yet. However, none of them were found to have hypercalcemia in the laboratory evaluation. Treatment was started with low-dose fluconazole, which inhibits enzymes (including 25-hydroxylases and 1-α-hydroxylase) synthesizing vitamin D. After a month of treatment at a dose of 50 mg/day, no change was observed in the patient's calcium values. Follow-up with calcium-restricted diet and adequate oral hydration therapy was planned. Conclusion Idiopathic infantile hypercalcemia may manifest later or diagnosed later in adulthood. Genetic examination should be considered in adult patients in whom other causes of PTH-independent hypercalcemia have been excluded.Table 1.Patient's laboratory parameters