Introduction: Hypercalcemia can be caused by a variety of pathologies/factors. Vitamin D plays a central role in calcium homeostasis, where a tight control of its metabolism is necessary. Inadequate 24-hydroxylase-enzime (CYP24A1) activity leads to failure of 25-hydroxyvitamin and 1,25-dihydroxy-vitamin D3 inactivation, resulting in hypercalcemia.
Case report: An asymptomatic, 22-year-old woman was admitted in an Endocrinology appointment for evaluation of persisting hypercalcemia (10.511.6 mg/dl). Medical history revealed that the patient suffered a transient period of polyuria during childhood (45-years-old), diagnosed as recurrent cystitis. Currently without any known disease or medication. Born to nonconsaguineous parents; no other known familial cases. Further evaluation revealed: hypercalciuria, suppressed parathyroid hormone (PTH) and elevated 1,25-dihydroxy-vitamin D3; with normal levels of 25-hydroxyvitamin D3, serum phosphorus, creatinine and angiotensin converting enzyme. A renal ultrasound demonstrated medullary nephrocalcinosis. Sequence analysis of the CYP24A1 gene was performed, revealing the patient has two mutations in heterozygosity: c.1186C>T(p.Arg396Trp) and c.1226T>C(p.Leu409Ser). Analytic and genetic study of first-degree relatives was performed. The father is homozygous for the c.1186C>T(p.Arg396Trp) mutation, with decreased level of PTH. The mother is a carrier of the c.1226T>C(p.Leu409Ser) mutation, in heterozygosity; with normal analytic evaluation. A 15-year-old sister has the same two mutations as the patient, with hypercalcemia, decreased PTH and medullary nephrocalcinosis. A low-calcium diet, avoidance of vitamin D supplements and sun protection were recommended.
Conclusion: Idiopathic infantile hypercalcemia is an autosomal recessively inherited disease, with an unknown prevalence. This particular case allows emphasizing two main problematics. Firstly, the diagnosis of the underlying cause of hypercalcemia in Endocrinology turns out to be more complex, as the vitamin D has an important role besides PTH. Secondly, the identification of patients with this disease as an at-risk group brings a new aspect to the debate concerning vitamin D supplementation. More studies are necessary to understand the severity of this disease over time.