Bone Abstracts

Background: Idiopathic infantile hypercalcemia (IIH) is a rare cause of infantile hypercalcemia characterized by failure to thrive, vomiting, dehydration, and nephrocalcinosis. This condition has recently been associated with mutations in the CYP24A1 gene, which encodes 25-hydroxyvitamin D3 24-hydroxylase, the key enzyme of 1,25-dihydroxyvitamin D3 degradation. Until now, only 13 cases genetically tested for IIH have been reported in the literature.

Case report: We reported a case of a 10-month-old male infant, who was referred to our Pediatric Clinic because of failure to thrive. His weight was 6560 g (between −3 S.D and −2 S.D below the mean) and length was 69 cm (between −1 S.D and the mean). Laboratory studies revealed severe hypercalcemia (4.58 mmol/l), hypercalciuria (3.05 u ca/u cr), suppressed parathyroid hormone (0.106 pmol/l) and elevated plasma levels of 25-hydroxyvitamin D3 (169.48 nmol/l). His renal ultrasonography scan revealed marked medullary nephrocalcinosis.

We started a conservative therapy with i.v. rehydration, diuretics and i.v. neridronate (1 mg/kg), that normalized plasma calcium levels (2.7 mmol/l).

Karyotype excluded Wiliams syndrome. Additional tests excluded malignancy, chronic renal disease, hypoadrenocorticism, granulomatous disorders and osteolysis.

Molecular testing of the CYP24A1 gene revealed a homozygous deletion (E143del). Both parents were heterozygous for this mutation.

At subsequent checks, we observed an improvement of his growth velocity and a good weight gain.

In spite of bisphosphonate therapy, the patient maintained elevated plasma levels of osteocalcin (10.4 nmol/l), bone alkaline phosphatase (92 μg/l) and the C-terminal telopeptide of type I collagen (1210 ng/l).

Discussion: We report the case of an infant affected by IHH, caused by a homozygous CYP24A1 gene mutation, who normalized plasma calcium levels and growth velocity with conservative therapy.

The prognosis of these patients is not still clearly known, but, considered the nephrocalcinosis and the high bone turnover markers, we suggest that a closely nephrologic and endocrinological follow-up is strictly necessary.