Emory College of Arts and Sciences, Emory University, Atlanta, GA, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Mol Genet Metab. 2023 Apr;138(4):107542. doi: 10.1016/j.ymgme.2023.107542. Epub 2023 Feb 21.
Classic and clinical variant galactosemia (CG/CVG) are allelic, autosomal recessive disorders that result from deficiency of galactose-1-P uridylyltransferase (GALT). CG/CVG has been reported globally among patients of diverse ancestries, but most large studies of outcomes have included, almost exclusively, patients categorized as White or Caucasian. As a first step to explore whether the cohorts studied are representative of the CG/CVG population at large, we sought to define the racial and ethnic makeup of CG/CVG newborns in a diverse population with essentially universal newborn screening (NBS) for galactosemia: the United States (US). First, we estimated the predicted racial and ethnic distribution of CG/CVG by combining the reported demographics of US newborns from 2016 to 2018 with predicted homozygosity or compound heterozygosity of pathogenic, or likely pathogenic, GALT alleles from the relevant ancestral groups. Incorporating some simplifying assumptions, we predicted that of US newborns diagnosed with CG/CVG, 65% should be White (non-Hispanic), 23% should be Black (non-Hispanic), 10% should be Hispanic, and 2% should be Asian (non-Hispanic). Next, we calculated the observed racial and ethnic distribution of US newborns diagnosed with CG/CVG using available de-identified data from state NBS programs from 2016 to 2018. Of the 235 newborns in this cohort, 41 were categorized as other or unknown. Of the remaining 194, 66% were White (non-Hispanic or ethnicity unknown), 16% were Black (non-Hispanic or ethnicity unknown),15% were Hispanic, and 2% were Asian (non-Hispanic or ethnicity unknown). This observed distribution was statistically indistinguishable from the predicted distribution. To the limits of our study, these data confirm the racial and ethnic diversity of newborns with CG/CVG in the US, demonstrate an approach for estimating CG/CVG racial and ethnic diversity in other populations, and raise the troubling possibility that current understanding of long-term outcomes in CG/CVG may be skewed by ascertainment bias of the cohorts studied.
经典型和临床变异型半乳糖血症 (CG/CVG) 是由半乳糖-1-磷酸尿苷酰转移酶 (GALT) 缺乏引起的常染色体隐性遗传疾病。CG/CVG 已在不同种族的患者中全球报道，但大多数大型结局研究几乎仅纳入被归类为白种人或高加索人的患者。作为探索所研究队列是否代表 CG/CVG 人群的第一步，我们试图确定在进行基本普遍的半乳糖血症新生儿筛查的多样化人群中 CG/CVG 新生儿的种族和民族构成：美国 (US)。首先，我们结合 2016 年至 2018 年美国新生儿的报告人口统计学数据，以及来自相关祖先群体的致病性或可能致病性 GALT 等位基因的预测纯合子或复合杂合子，估计 CG/CVG 的预测种族和民族分布。在纳入一些简化假设的情况下，我们预测在美国诊断为 CG/CVG 的新生儿中，65%应为白人（非西班牙裔），23%应为黑人（非西班牙裔），10%应为西班牙裔，2%应为亚洲人（非西班牙裔）。接下来，我们使用 2016 年至 2018 年州 NBS 计划提供的可用去识别数据，计算在美国诊断为 CG/CVG 的新生儿的观察种族和民族分布。在该队列的 235 名新生儿中，有 41 名被归类为其他或未知。在其余的 194 名中，66%为白人（非西班牙裔或种族未知），16%为黑人（非西班牙裔或种族未知），15%为西班牙裔，2%为亚洲人（非西班牙裔或种族未知）。这种观察到的分布与预测分布在统计学上无显著差异。在我们研究的范围内，这些数据证实了美国 CG/CVG 新生儿的种族和民族多样性，展示了一种在其他人群中估计 CG/CVG 种族和民族多样性的方法，并提出了一个令人不安的可能性，即目前对半乳糖血症长期结局的理解可能受到所研究队列的确定偏差的影响。
