Endocrine Abstracts

JOINT762

Infantile hypercalcemia-1 (HCINF1) is a rare disorder of mineral metabolism caused by homozygous loss-of-function variants of the CYP24A1 gene which induce an increase of serum 1, 25(OH)₂D3 concentration, and consequently hypercalcemia, hypercalciuria, and low-to-undetectable plasma PTH levels. The aim of this study was to evaluate the bone phenotype in a cohort of patients affected by HCINF1 disease followed at our outpatient clinic. We included 5 patients (1 female and 4 males) carrying homozygous (Group A) and 7 patients (3 females and 4 males) carrying heterozygous CYP24A1 variants (Group B). In group A, the median age was 26 (IQR: 25-52), while in group B, it was 30 years (IQR 30-60). No patient experienced clinical fragility fractures or morphometric fractures as assessed by DXA. One male patient aged 69 years of the group A and another male patient aged 63 years of the group B exhibited osteoporosis at 1/3 distal radius, with T-score: -3 and -3. 3, respectively. Both patients did not have risk factors for osteoporosis. Two of the 5 patients of group A had osteopenia at femur (both total and neck regions) and 1 patient showed osteopenia at 1/3 distal radius. Conversely, 1 of the 7 patients in group B exhibited osteopenia at lumbar spine. The remaining patients had normal BMD at all sites and normal trabecular bone score values. Regarding bone turnover biomarkers, all values were in the normal range. Specifically, in the group A the value of bone-specific alkaline phosphatase (BAP) was 13 mg/l in the female and the median of BAP was 15 mg/l (IQR: 13-16, 5) in males, while in group B the median was 12 mg/l (IQR: 11, 65-12) in females and 13 mg/l (IQR 11, 25-16, 25) in males. Osteocalcin levels were 20, 45 mg/l (IQR: 19, 13-23, 63) in group A and 11 mg/l (IQR 9, 5-29, 45) in group B. In group A, the value of serum CTX was 0, 36 mg/l in the female and the median value was 0, 464 mg/l (IQR: 0, 344-0, 667) in males while in group B CTX was 0, 186 mg/l (IQR 0, 125-0, 199) in females and the median was 0, 14 mg/l (IQR: 0, 133-0, 234) in males. Our findings seem to suggest that the BMD in homozygous patients with HCINF1 tend to be lower compared to heterozygous patients. Moreover, the levels of BAP, osteocalcin and sCTX are in the half/lower half of the reference range, this could reflect a low bone turnover secondary to low PTH levels, as occurs in hypoparathyroidism.