囊性纤维化筛查阳性不确定诊断（CFSPID）：意大利托斯卡纳的经验。

Cystic fibrosis screen positive inconclusive diagnosis (CFSPID): Experience in Tuscany, Italy.

机构信息

Cystic Fibrosis Centre, Department of Paediatric Medicine, Anna Meyer Children's University Hospital, Florence, Italy.

出版信息

J Cyst Fibros. 2019 Jul;18(4):484-490. doi: 10.1016/j.jcf.2019.04.002. Epub 2019 Apr 18.

DOI:10.1016/j.jcf.2019.04.002

PMID:31005549

Abstract

OBJECTIVE

The implementation of cystic fibrosis (CF) newborn screening (NBS) has led to identification of infants with a positive NBS test but inconclusive diagnosis classified as "CF screen positive, inconclusive diagnosis" (CFSPID). We retrospectively evaluated the prevalence and clinical outcome of CFSPID infants diagnosed by 2 NBS algorithms in the period from 2011 to 2016 in the Tuscany region of Italy.

METHODS

In 2011-2016, we assessed the diagnostic impact of DNA analysis on the NBS 4-tier algorithm [immunoreactive trypsin (IRT) - meconium lactase - IRT2 - sweat chloride (SC)]. All CFSPID patients repeated SC testing every 6 months, and CFTR gene analysis was performed (detection rate 98%). We reclassified children as: CF diagnosis in presence of at least 2 pathological SC results; healthy carrier or healthy in presence of at least 2 normal SC results for age and either 1 or 0 CF-causing mutations, respectively.

RESULTS

We identified 32 CF and 50 CFSPID cases: 20/50 (40%) were diagnosed only by the IRT-DNA-SC algorithm and 16/50 (32%) only by IRT-meconium lactase-IRT2-SC. Both protocols identified the remaining 14 cases (28%). Thirty-seven of 50 (74%) CFSPID patients had a conclusive diagnosis on December 31, 2017:5 (10%) CF, 17 (34%) healthy and 15 (30%) healthy carriers; 13/50 (26%) cases were asymptomatic with persistent intermediate SC and followed as CFSPID (CF:CFSPID ratio 2.85:1).

CONCLUSIONS

In 6 years, the CF:CFSPID ratio modified from 0.64:1 to 2.85:1, and 10% of CFSPID cases progressed to CF. Genetic analysis improved positive predictive value and identified a higher number of CFSPID infants progressing to CF.

摘要

目的

囊性纤维化（CF）新生儿筛查（NBS）的实施导致了一批通过 NBS 检测但诊断不明确的婴儿的出现，被归类为“CF 筛查阳性，诊断不确定”（CFSPID）。我们回顾性评估了 2011 年至 2016 年期间意大利托斯卡纳地区通过两种 NBS 算法诊断的 CFSPID 婴儿的患病率和临床结局。

方法

在 2011 年至 2016 年期间，我们评估了 DNA 分析对 NBS 4 级算法（免疫反应性胰蛋白酶（IRT）-粪乳糖酶-IRT2-汗液氯化物（SC））的诊断影响。所有 CFSPID 患者每 6 个月重复进行 SC 检测，同时进行 CFTR 基因突变分析（检出率 98%）。我们重新分类儿童如下：存在至少 2 次异常 SC 结果时诊断为 CF；存在至少 2 次正常 SC 结果且年龄匹配，并且存在 1 或 0 个 CF 致病突变时，分别归类为健康携带者或健康。

结果

我们共发现 32 例 CF 和 50 例 CFSPID 病例：20/50（40%）仅通过 IRT-DNA-SC 算法诊断，16/50（32%）仅通过 IRT-粪乳糖酶-IRT2-SC 算法诊断。两种方案均能发现其余 14 例（28%）。2017 年 12 月 31 日，50 例 CFSPID 患者中有 37 例（74%）得出明确诊断：5 例（10%）为 CF，17 例（34%）为健康，15 例（30%）为健康携带者；13 例（26%）无症状，SC 持续处于中间值，作为 CFSPID 继续随访（CF：CFSPID 比值为 2.85:1）。