CYP24A1 and SLC34A1 mutations in five cases with idiopathic infantile hypercalcemia

Abstract

Abstract Backgrounds Idiopathic infantile hypercalcemia (IIH) is a rare hereditary disorder caused by CYP24A1 and SLC34A1 gene mutations. In this study, the clinical manifestations and molecular aspects of five new Chinese patients were investigated. Results Four patients showed hypercalcemia, hypercalciuria, decreased PTH and bilateral medullary nephrocalcinosis in early infancy. Their clinical symptoms and biochemical abnormalities improved after intensive hydration, furosemide and oral phosphorus treatment, except one patient needed salmon calcitonin injection. All patients remained bilateral medullary nephrocalcinosis. One patient admitted at 11 years old presented arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. She had history of nausea, poor appetite and growing when infancy. Gene analysis showed two have compound heterozygous mutations of CYP24A1, one patient with monoallelic CYP24A1 variant, and two with monoallelic SLC34A1 variant. Four CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and two SLC34A1 variants (c.1322A > G and c.1697_1698insT) were first reported. Conclusions CYP24A1 and SLC34A1 gene mutations are genetic cause of idiopathic infantile hypercalcemia. Monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH are varying with onset age. Hypercalcemia may not the necessarily after infancy and the patients with nephrolithiasis either in older children or adults may consider IIH.