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Abstract：
OBJECTIVE: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated.
METHODS: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively.
RESULTS: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients.
CONCLUSIONS: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.
METHODS: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively.
RESULTS: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients.
CONCLUSIONS: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.
摘要：
目的：特发性婴儿高钙血症（IIH）是一种罕见的PTH非依赖性高钙血症。CYP24A1和SLC34A1基因突变导致两种形式的遗传性IIH。在这项研究中,研究了6例新中国患者的临床表现和分子方面。
方法：回顾性分析6例特发性小儿高钙血症的临床表现和实验室检查。
结果：5例患者被诊断为高钙血症，高钙尿症,和双侧髓样肾钙化。治疗后临床症状及生化异常改善。一名患者在11岁时出现动脉高血压，高钙尿症和肾钙化，但血清钙正常.基因分析显示2例患者有CYP24A1复合杂合突变,1例患者有CYP24A1单等位基因变异,3例患者具有单等位基因SLC34A1变体。四个新的CYP24A1变体（c.116G>C，c.287T>A，c.476G>A和c.1349T>C）和三个新颖的SLC34A1变体（c.1322A>G，在这些患者中发现了c.1697_1698insT和c.1726T>C）。
结论：CYP24A1或SLC34A1基因的单等位基因变异与症状性高钙血症有关，高钙尿症和肾钙化。IIH的表现随发病年龄而变化。婴儿期后可能不一定存在高钙血症，年龄较大的儿童或成人的肾结石患者应考虑IIH。
方法：回顾性分析6例特发性小儿高钙血症的临床表现和实验室检查。
结果：5例患者被诊断为高钙血症，高钙尿症,和双侧髓样肾钙化。治疗后临床症状及生化异常改善。一名患者在11岁时出现动脉高血压，高钙尿症和肾钙化，但血清钙正常.基因分析显示2例患者有CYP24A1复合杂合突变,1例患者有CYP24A1单等位基因变异,3例患者具有单等位基因SLC34A1变体。四个新的CYP24A1变体（c.116G>C，c.287T>A，c.476G>A和c.1349T>C）和三个新颖的SLC34A1变体（c.1322A>G，在这些患者中发现了c.1697_1698insT和c.1726T>C）。
结论：CYP24A1或SLC34A1基因的单等位基因变异与症状性高钙血症有关，高钙尿症和肾钙化。IIH的表现随发病年龄而变化。婴儿期后可能不一定存在高钙血症，年龄较大的儿童或成人的肾结石患者应考虑IIH。
