Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births)  characterized by increased vitamin D sensitivity , with symptomatic severe hypercalcemia.
IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis .
The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D , and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology .
The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis .
We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis.
Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.
Keywords: CYP24A1, Hypercalcemia, Infantile Idiopatic Hypercalcemia, Vitamin D, Nephrocalcinosis