Hall Patricia L, Li Hong, Hagar Arthur F, Jerris S Caleb, Wittenauer Angela, Wilcox William
Department of Human Genetics Atlanta, Emory University, Atlanta, GA 30322, USA.
Georgia Department of Public Health, Atlanta, GA 30033, USA.
Int J Neonatal Screen. 2020 Oct 23;6(4):81. doi: 10.3390/ijns6040081.
We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools. Second-tier test results were reported as normal or abnormal based on a cutoff for the single analyte, C26:0 LPC. Eleven cases were reported as abnormal based on second-tier test results. One male with ALD was identified, and two females with peroxisomal biogenesis disorders were also identified. A single female case remains unresolved, due to a loss to follow up after a negative molecular test result for gene sequencing. The positive predictive value for confirmed, clinically relevant disorders during this pilot study was 27.3%. Challenges identified during the study period were based around coverage for confirmatory testing, particularly if family members needed molecular testing, which is an ongoing issue with newborn screening in Georgia. We also encountered issues with the follow up for a patient who remained asymptomatic. Due to the different timelines involved with clinical findings in ALD, follow-up coordination may be more difficult, particularly if the child identified by newborn screening (NBS) is the only member of the family affected, or able to be tested.
我们采用一种两层策略对51,081名新生儿进行了X连锁肾上腺脑白质营养不良（ALD）筛查，该策略用于定量极长链溶血磷脂酰胆碱（LPC）。我们的检测策略采用流动注射串联质谱法对LPC进行一级分析，并使用液相色谱串联质谱法对C26:0 LPC进行二级定量。使用我们基于四种LPC测量值和分析后工具的一级算法，有364个样本被认为异常。二级检测结果根据单一分析物C26:0 LPC的临界值报告为正常或异常。基于二级检测结果，有11例报告为异常。鉴定出1例患有ALD的男性，还鉴定出2例患有过氧化物酶体生物发生障碍的女性。由于基因测序的分子检测结果为阴性后失访，1例女性病例仍未得到解决。在这项初步研究中，确诊的临床相关疾病的阳性预测值为27.3%。研究期间发现的挑战围绕确认性检测的覆盖范围，特别是如果家庭成员需要分子检测，这是佐治亚州新生儿筛查中一个持续存在的问题。我们还遇到了对一名无症状患者进行随访的问题。由于ALD临床发现涉及不同的时间线，随访协调可能更加困难，特别是如果通过新生儿筛查（NBS）确定的儿童是家庭中唯一受影响或能够接受检测的成员。
