Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake
Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake
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DOI：
10.1007/s00467-014-2889-1
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发表时间：
2015-01-01
影响因子：
3
通讯作者：
Holtzman, Eli J.
中科院分区：
文献类型：
--
作者：
Dinour, Dganit;Davidovits, Miriam;Holtzman, Eli J.
高钙血症是由许多不同的条件，并可能导致严重的并发症。编码维生素D-24-羟化酶的CYP 24 A1的功能丧失突变最近在特发性婴儿高钙血症和成人肾结石病中被确定。本研究的目的是调查婴儿和母亲的高钙血症的遗传学和临床特征，我们研究了四个不相关的以色列家庭成员与高钙血症，即一名妇女在怀孕期间和分娩后，三个婴儿。临床和生化数据从先证者的病历中获得。从外周血中提取基因组DNA并进行CYP 24 A1测序。在婴儿和孕妇中出现与推荐剂量维生素D摄入相关的典型高钙血症症状。发现了4种不同的CYP 24 A1功能丧失突变，其中2种为首次报道（p.Trp134Gly和p.Glu315*）。家系1和家系2的婴儿分别为复合杂合子，家系3的婴儿和孕妇均为纯合子，这是首次报道由CYP 24 A1突变引起的母亲高钙血症，表明不仅婴儿有患这种并发症的风险。我们的研究结果强调了在这个广泛使用维生素D补充剂的时代，对这种最近发现的高钙症进行识别、基因诊断和适当治疗的重要性。
Hypercalcemia is caused by many different conditions and may lead to severe complications. Loss-of-function mutations of CYP24A1, encoding vitamin D-24-hydroxylase, have recently been identified in idiopathic infantile hypercalcemia and in adult kidney stone disease. The aim of this study was to investigate the genetics and clinical features of both infantile and maternal hypercalcemia.We studied members of four unrelated Israeli families with hypercalcemia, namely, one woman during pregnancy and after delivery and three infants. Clinical and biochemical data were obtained from probands' medical charts. Genomic DNA was isolated from peripheral blood and CYP24A1 was sequenced.Typical symptoms of hypercalcemia associated with the intake of recommended doses of vitamin D developed in the infants and pregnant woman. Four different loss-of-function CYP24A1 mutations were identified, two of which are reported here for the first time (p.Trp134Gly and p.Glu315*). The infants from families 1 and 2, respectively, were found to be compound heterozygotes, and the infant from family 3 and the pregnant woman were found to be homozygous.This is the first report of maternal hypercalcemia caused by a CYP24A1 mutation, showing that not only infants are at risk for this complication. Our findings emphasize the importance of recognition, genetic diagnosis and proper treatment of this recently identified hypercalcemic disorder in this era of widespread vitamin D supplements.