新生儿筛查后囊性纤维化的诊断不明确。

Inconclusive diagnosis of cystic fibrosis after newborn screening.

作者信息

Ooi Chee Y, Castellani Carlo, Keenan Katherine, Avolio Julie, Volpi Sonia, Boland Margaret, Kovesi Tom, Bjornson Candice, Chilvers Mark A, Morgan Lenna, van Wylick Richard, Kent Steven, Price April, Solomon Melinda, Tam Karen, Taylor Louise, Malitt Kylie-Ann, Ratjen Felix, Durie Peter R, Gonska Tanja

机构信息

Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Sydney Children's Hospital Randwick, Sydney, Australia; Division of Gastroenterology, Hepatology, and Nutrition.

Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy;

出版信息

Pediatrics. 2015 Jun;135(6):e1377-85. doi: 10.1542/peds.2014-2081. Epub 2015 May 11.

DOI:10.1542/peds.2014-2081

PMID:25963003

Abstract

OBJECTIVES

To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations.

METHODS

Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life.

RESULTS

Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 [105-199] μg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients.

CONCLUSIONS

A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.

摘要

目的

对通过新生儿筛查（NBS；“囊性纤维化筛查阳性，诊断不明确”[CFSPID]）确诊的囊性纤维化（CF）诊断不明确的婴儿进行前瞻性研究，以观察疾病表现。

方法

对来自8个CF中心的基于NBS诊断为CFSPID和CF的婴儿进行前瞻性评估和监测。比较CF和CFSPID患者之间以及在生命的前3年中符合CF标准（CFSPID→CF）和不符合CF标准（CFSPID→CFSPID）的CFSPID患者之间的基因型、表型、重复汗液试验、血清胰蛋白酶原和微生物学数据。

结果

共纳入82例CFSPID患者和80例CF患者。不同中心CFSPID与CF的比例在1:1.4至1:2.9之间。各组间CFTR突变率无差异；96%的CFSPID患者和93%的CF患者有2种突变。CFSPID患者的NBS免疫反应性胰蛋白酶原水平显著低于CF患者（中位数[四分位间距]：77[61 - 106] vs 144[105 - 199]μg/L；P <.0001）。在CFSPID患者中，铜绿假单胞菌和嗜麦芽窄食单胞菌的分离率分别为12%和5%。82例CFSPID患者中有9例（11%）被诊断为CF（基因型和异常汗液氯化物 = 3；仅基因型 = 4；仅异常汗液氯化物 = 2）。CFSPID→CF患者汗液氯化物异常时的平均（标准差）年龄为21.3（13.8）个月。CFSPID→CF患者的系列汗液氯化物水平（P <.0001）和血清胰蛋白酶原水平（P =.009）显著高于CFSPID→CFSPID患者。