Abstract：
OBJECTIVE: Newborn screening (NBS) for inborn errors of metabolism (IEMs) has been successfully implemented in China. However, the data on the IEM profiles in many regions are lacking. This study aimed to report the incidence, disease spectrum, and genetic profile of IEMs in northern China.
METHODS: A total of 36,590 newborns were screened using tandem mass spectrometry between January 2016 and April 2022. Newborns with positive results were referred for confirmatory testing.
RESULTS: Ten patients were confirmed to have IEMs, with an overall incidence of 1:3,539 in the Rizhao region. Five types of IEMs were detected, including four patients with propionic acidemia (PA), three patients with methylmalonic acidemia (MMA), one of each with citrin deficiency, primary carnitine deficiency, and isobutyryl-CoA dehydrogenase deficiency. PA was the most common IEM, with an unexpectedly high incidence of 1:8,848, followed by MMA, with an incidence rate of 1:11,797. All patients had abnormal screening markers and harbored biallelic variants in their respective causative genes. Two novel PCCB variants (c.505G>A and c.1123_1124insG) were identified in patients with PA. In silico analyses predicted that these two variants were potentially pathogenic.
CONCLUSIONS: This study preliminarily clarified the incidence, disease spectrum, and genetic profile of IEMs in the Rizhao region. PA is the most common IEM and MMA is the second most common in our region. The two novel identified PCCB variants further expand the variant spectrum of PA. More attention should be paid to NBS, early diagnosis, and management of PA and MA.
METHODS: A total of 36,590 newborns were screened using tandem mass spectrometry between January 2016 and April 2022. Newborns with positive results were referred for confirmatory testing.
RESULTS: Ten patients were confirmed to have IEMs, with an overall incidence of 1:3,539 in the Rizhao region. Five types of IEMs were detected, including four patients with propionic acidemia (PA), three patients with methylmalonic acidemia (MMA), one of each with citrin deficiency, primary carnitine deficiency, and isobutyryl-CoA dehydrogenase deficiency. PA was the most common IEM, with an unexpectedly high incidence of 1:8,848, followed by MMA, with an incidence rate of 1:11,797. All patients had abnormal screening markers and harbored biallelic variants in their respective causative genes. Two novel PCCB variants (c.505G>A and c.1123_1124insG) were identified in patients with PA. In silico analyses predicted that these two variants were potentially pathogenic.
CONCLUSIONS: This study preliminarily clarified the incidence, disease spectrum, and genetic profile of IEMs in the Rizhao region. PA is the most common IEM and MMA is the second most common in our region. The two novel identified PCCB variants further expand the variant spectrum of PA. More attention should be paid to NBS, early diagnosis, and management of PA and MA.
摘要：
目的：新生儿先天性代谢异常（IEM）筛查（NBS）已在中国成功实施。然而,许多地区缺乏IEM配置文件的数据。本研究旨在报告发病率，疾病谱,和中国北方IEM的遗传概况。
方法：在2016年1月至2022年4月之间，使用串联质谱法对总共36,590名新生儿进行了筛查。结果为阳性的新生儿被转介进行验证性测试。
结果：10例患者被证实患有IEM，日照地区总体发病率为1:3,539。检测到五种类型的IEM，包括四名丙酸血症（PA）患者，3例甲基丙二酸血症（MMA），每个人都有一个citrin缺乏症，原发性肉碱缺乏症，和异丁酰辅酶A脱氢酶缺乏症。PA是最常见的IEM,意外的高发病率为1:8,848，其次是MMA，发病率为1:11,797。所有患者都有异常的筛选标记，并在各自的致病基因中包含双等位基因变异。在PA患者中鉴定出两种新的PCCB变体（c.505G>A和c.1123_1124insG）。计算机分析预测这两种变体具有潜在的致病性。
结论：本研究初步阐明了发病率，疾病谱,日照地区IEM的遗传概况。PA是我们地区最常见的IEM，MMA是第二常见的IEM。这两个新鉴定的PCCB变体进一步扩展了PA的变体谱。应该更加关注国家统计局，早期诊断,以及PA和MA的管理。
方法：在2016年1月至2022年4月之间，使用串联质谱法对总共36,590名新生儿进行了筛查。结果为阳性的新生儿被转介进行验证性测试。
结果：10例患者被证实患有IEM，日照地区总体发病率为1:3,539。检测到五种类型的IEM，包括四名丙酸血症（PA）患者，3例甲基丙二酸血症（MMA），每个人都有一个citrin缺乏症，原发性肉碱缺乏症，和异丁酰辅酶A脱氢酶缺乏症。PA是最常见的IEM,意外的高发病率为1:8,848，其次是MMA，发病率为1:11,797。所有患者都有异常的筛选标记，并在各自的致病基因中包含双等位基因变异。在PA患者中鉴定出两种新的PCCB变体（c.505G>A和c.1123_1124insG）。计算机分析预测这两种变体具有潜在的致病性。
结论：本研究初步阐明了发病率，疾病谱,日照地区IEM的遗传概况。PA是我们地区最常见的IEM，MMA是第二常见的IEM。这两个新鉴定的PCCB变体进一步扩展了PA的变体谱。应该更加关注国家统计局，早期诊断,以及PA和MA的管理。
