High Prevalence of Kidney Cysts in Patients With CYP24A1 Deficiency.
High Prevalence of Kidney Cysts in Patients With CYP24A1 Deficiency.
复制标题
DOI：
10.1016/j.ekir.2021.04.030
复制
发表时间：
2021-07
影响因子：
6
通讯作者：
Chebib FT
中科院分区：
文献类型：
--
作者：
Hanna C;Potretzke TA;Cogal AG;Mkhaimer YG;Tebben PJ;Torres VE;Lieske JC;Harris PC;Sas DJ;Milliner DS;Chebib FT
CYP 24 A1基因的功能丧失变体会导致一种罕见的遗传性疾病，其特征是24-羟化酶活性降低、血清1，25-二羟基胆钙化醇水平升高、高钙血症、高钙尿症以及肾钙质沉着症和/或肾结石。我们中心的一项单一病例研究首次报告了CYP 24 A1缺乏症患者的肾囊肿。然而，CYP 24 A1缺乏和肾囊肿之间的可能关联尚未被描述。对确诊或疑似CYP 24 A1缺乏且肾脏成像可用的患者进行回顾性分析。在16例确诊致病性变异的患者中，38%为男性，31%为儿童，遗传确认的中位年龄为38岁（范围1-66岁），无囊性肾病家族史。所有病例均存在髓质和/或皮髓质交界处囊肿。首次发现囊肿的中位年龄为37岁（范围3-60岁）。每例患者的囊肿平均数和中位数分别为5.3和2.5（范围1-37）。另外5例疑似但未证实致病性变异的患者中有4例有囊肿。在55%和67%的确诊和疑似致病性变异患者中，大小≥5 mm的囊肿数量分别高于年龄和性别匹配对照人群的第97.5百分位数。在80%确诊为CYP 24 A1缺陷的儿童中发现至少1个囊肿（大小≥5 mm）。这些观察结果强烈表明CYP 24 A1缺乏和肾囊肿之间的关联。需要进一步的研究来评估CYP 24 A1、维生素D代谢和/或高钙尿在囊肿形成中的作用，以及囊肿是否会加重慢性肾脏疾病或改变肾钙质沉着和结石风险。
Loss-of-function variants in the CYP24A1 gene cause a rare hereditary disease characterized by reduced 24-hydroxylase enzyme activity, increased serum 1,25-dihydroxycholecalciferol levels, hypercalcemia, hypercalciuria, and nephrocalcinosis and/or nephrolithiasis. Kidney cysts in patients with CYP24A1 deficiency were first reported in a single case study from our center. However, a possible association between CYP24A1 deficiency and kidney cysts has not been described. Retrospective analysis of patients with confirmed or suspected CYP24A1 deficiency and available kidney imaging. Among 16 patients with confirmed pathogenic variants, 38% were male and 31% were children, the median age at genetic confirmation was 38 years (range 1–66), and none had a family history of cystic kidney disease. Medullary and/or corticomedullary junction cysts were present in all cases. The median age at first detected cyst was 37 years (range 3–60). The mean and median number of cysts per patient were 5.3 and 2.5 (range 1–37), respectively. Four of 5 further patients with suspected but unconfirmed pathogenic variants had cysts. The number of cysts ≥5 mm in size was above the 97.5th percentile of an age- and sex-matched control population in 55% and 67% of patients with confirmed and suspected pathogenic variants, respectively. At least 1 cyst (≥5 mm in size) was found in 80% of children with confirmed CYP24A1 deficiency. These observations strongly suggest an association between CYP24A1 deficiency and kidney cysts. Further studies are needed to evaluate the role of CYP24A1, vitamin D metabolism, and/or hypercalciuria in cyst formation, and whether cysts exacerbate chronic kidney disease or modify nephrocalcinosis and stone risk.
登录
查看更多内容
影响因子：
13.6
作者：
Iwaki, Takayuki;Sandoval-Coopel, Mayra J.;Castellino, Francis J.
通讯作者：
Castellino, Francis J.
影响因子：
13.2
作者：
Rule, Andrew D.;Sasiwimonphan, Kewalee;Vrtiska, Terri J.
通讯作者：
Vrtiska, Terri J.
影响因子：
6.2
作者：
Woods, Gina N.;Saitman, Alec;Chi, Nai-Wen
通讯作者：
Chi, Nai-Wen
影响因子：
158.5
作者：
Schlingmann, Karl P.;Kaufmann, Martin;Konrad, Martin
通讯作者：
Konrad, Martin
影响因子：
5.8
作者：
Tebben, Peter J.;Milliner, Dawn S.;Kumar, Rajiv
通讯作者：
Kumar, Rajiv