Endocrine Abstracts

JOINT2355

CYP24A1, encoding the vitamin D-24-hydroxylase, regulates the catabolism of 1,25-(OH)2vitamin D. Inactivating biallelic mutations of the CYP24A1 gene are associated with elevated serum 1,25(OH)2vitamin D concentrations, hypercalcemia, hypercalciuria, nephrolithiasis and suppressed PTH concentrations. We describe the clinical and molecular basis of long-standing hypercalcemia and nephrocalcinosis in a young adult. The patient is a 19-year-old male presented for PTH-independent hypercalcemia (serum total calcium 11.6 mg/dl, serum PTH 2.6 pg/ml) and nephrocalcinosis. He had a history of recurrent episodes of vomiting and constipation in childhood, when he was supplemented with vitamin D. From the age of 13, annual blood tests have been performed, revealing mild hypercalcemia and 25OH vitamin D values between 39-56 ng/ml. Family history was relevant for high normal serum calcium (mother) and nephrolithiasis (grandmother). The patient’s biochemistry in our clinic: serum calcium 11 mg/dl, urinary calcium 400 mg/24hrs, creatinine 1.22 mg/dl, PTH 2.4 pg/ml, 25OH-vitamin D 39 ng/ml, 1,25(OH)2vitamin D 66 pg/ml; serum phosphate 3.3 mg/dl, urinary phosphate 700 mg/24hrs, FGF23 224 pg/ml, normal PTHrP and ACE. Bone turnover markers were: cross laps 0.69 ng/ml, osteocalcin 50.4 ng/ml, P1NP 86.3ng/ml and he has a high bone mass (DXA): L1-L4 Z-score = 2.6 DS, femoral neck Z score = 3.8 DS, total hip Z-score = 4.2 DS. Analysis of whole exome sequence variants revealed that the patient is heterozygous for CYP24A1 c.1186C>T, p. (Arg396Trp) and c.428_430del, p(Glu143del), which are both pathogenic. With low-calcium diet, high water intake and limited sunlight exposure, after 3 months, the biochemistry improved: serum calcium 9.7 mg/dl, urinary calcium 360 mg/24hrs, creatinine 1.03 mg/dl, PTH 6.7 pg/ml, 25OHvitamin D 24 ng/ml, 1,25(OH)2vitamin D 62 pg/ml.

Conclusion: CYP24A1 mutations should be considered in the differential diagnosis of PTH-independent hypercalcemia in both children and adults.