BACKGROUND:Generalized arterial calcification of infancy has been reported to be frequently lethal, and the efficiency of any therapy, including bisphosphonates, is unknown. A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy. METHODS AND RESULTS:We performed a multicenter genetic study and retrospective observational analysis of 55 subjects affected by generalized arterial calcification of infancy to identify prognostic factors. Nineteen (34%) patients survived the critical period of infancy. In all 8 surviving patients tested, hypophosphatemia due to reduced renal tubular phosphate reabsorption developed during childhood. Eleven of 17 (65%) patients treated with bisphosphonates survived. Of 26 patients who survived their first day of life and were not treated with bisphosphonates only 8 (31%) patients survived beyond infancy. Forty different homozygous or compound heterozygous mutations, including 16 novel mutations in ENPP1, were found in 41 (75%) of the 55 patients. Twenty-nine (71%) of these 41 patients died in infancy (median, 30 days). Seven of the 14 (50%) patients without ENPP1 mutations died in infancy (median, 9 days). When present on both alleles, the mutation p.P305T was associated with death in infancy in all 5 cases; otherwise, no clear genotype-phenotype correlation was seen. CONCLUSION:ENPP1 coding region mutations are associated with generalized arterial calcification of infancy in approximately 75% of subjects. Except for the p.P305T mutation, which was universally lethal when present on both alleles, the identified ENPP1 mutations per se have no discernable effect on survival. However, survival seems to be associated with hypophosphatemia linked with hyperphosphaturia and also with bisphosphonate treatment.
背景: 广泛性动脉钙化的初期报告往往致命，和每种疗法，包括二膦酸盐，尚不清楚。磷高效饮食显著增加生存的 NPP1 缺失小鼠模型的广泛性动脉钙化的起步阶段。 方法和结果: 我们做一个基因的多中心临床研究和 55 回顾性观察分析问题的广泛性动脉钙化的起步阶段确定预后因素。十九 (34%) 病人存活的关键时期的第一步。各月幸存病人测试，低磷酸盐血症与降低磷酸肾小管重吸收发达的渴望。月之十一 (65%) 患者二膦酸盐活了下来。26 的病人幸存下来的第一天的生活并没有处理二膦酸盐只月 (31%) 病人存活超过刚刚起步。40 不同纯合子或复合杂合子突变，包括 16 nov el ENPP1 突变，被发现在 41 (75%) 55 的病人。29 (71%) 其中 41 病人死在婴儿期 (中位数，30 天)。七个月 (50%) 突变患者 ENPP1 死在婴儿期 (中位数，月天)。当出现两个等位基因，突变 p.P305T 与死亡的婴儿在所有军案件; 否则，没有明确的基因型-表型相关被看到。 结论: ENPP1 编码区突变是广义的动脉钙化的阶段中大约 75% 的主题。除第 P305T 突变，受到普遍致死时出现两个等位基因，确定 ENPP1 突变的生存本身没有明显影响。然而，生存似乎与低磷酸盐血症与高磷酸盐尿以及 bisphosphonate 治疗。
Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy.
Hypophosphatemia 英 /haipəufɔsfə'ti:miə/
释 义 n. 血磷酸盐过少；低磷酸盐血
例 句 Objective To study the relation between postoperative total parenteral nutrition(TPN) and hypophosphatemia and relation between hypophosphatemia and infection following gastrointestinal damage. 目的探讨胃肠损伤术后全静脉营养和低磷血症的关系以及低磷血症和胃肠损伤术后并发感染的关系。