Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as “healthy heterozygotes” or “unaffected carriers” should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with “genotype-to-risk.” In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.

常染色体隐性遗传病的杂合子（携带者）状态传统上被认为对个人健康没有意义，但这一假设受到越来越多证据的挑战。几种常染色体隐性遗传疾病和一些 X 连锁疾病的携带者可能面临纯合子中的病理表现的风险。这篇小型综述概述了有关推荐的统一筛查小组中两种常见常染色体隐性遗传疾病携带者的健康风险的文献：镰状细胞病 [镰状细胞性状 (SCT)] 和囊性纤维化 (CF)。我们还考虑和评论新生儿血液筛查 (NBS) 的生物伦理和政策影响。杂合子的健康风险虽然对个体而言相对较低，但通常受内在因素的影响（例如，其他基因组变异或合并症）和外在（环境）因素，这为个性化基因组医学和风险咨询提供了机会。然而，它们对制定筛查/随访政策和遗传咨询提出了特殊挑战，特别是在通过 NBS 识别和报告杂合子状态之后。尽管需要进行更多的研究，但迄今为止对 SCT 和 CF 文献的这一小型回顾使我们建议在有关 NBS 结果的交流中应取代诸如“健康杂合子”或“未受影响的携带者”之类的笼统术语，以支持更细致入微的范式用“基因型风险”设定健康结果的预期。在 NBS 的分子时代，很明显，公共卫生需要为全方位的应用遗传学做好更好的准备。