Background

Currently, healthcare systems worldwide are actively discussing the implementation of genomic analysis technology in newborn screening to identify genetic diseases that threaten the lives of newborns at an early stage. Existing newborn screening methods involve the chemical analysis of proteins or metabolites in dried blood spots. In the United States, screening for 66 diseases is recommended, but France screens for only 16, and the United Kingdom for 10, resulting in significant variations between countries. The existing screening, which focuses primarily on metabolic disorders, has limitations in early diagnosis of rare and life-threatening genetic diseases.

Familial Hemophagocytic Lymphohistiocytosis (HLH) is a prime example. This disease is accompanied by severe fever and inflammation, and without proper treatment, it can lead to death within a few months. Due to its rarity and diverse symptoms, delayed diagnosis or misdiagnosis is common, threatening the lives of affected infants.

To overcome these challenges, researchers worldwide have proposed Newborn Genomic Screening (NGS) as an alternative, which involves directly analyzing the DNA of newborns. With the development and cost reduction of Whole-Genome Sequencing (WGS) technology, large-scale pilot studies have begun, and genomic screening is expected to target hundreds of genetic diseases, offering opportunities for preventive treatment, surpassing the capabilities of existing screening methods.

Key Findings

Large-scale newborn genomic screening studies have demonstrated the potential to complement the limitations of existing screening methods. The GUARDIAN study in the United States aims to enroll 100,000 infants and perform WGS. Preliminary results from the first 15,000 participants showed that WGS confirmed 411 (2.7%) newborns with genetic diseases. The majority of the identified diseases were rare diseases not included in existing screening programs, and some infants were saved through immediate bone marrow transplantation.

The BabyScreen+ study in Australia also reported significant results. The study analyzed 1,000 newborns for 605 treatable genes and identified genetic diseases in 1.6% of infants. Giselle Gata, a participant in the study, had an HLH variant detected, and the infant successfully underwent a bone marrow transplant within 6 months of birth. The BabyDetect study in Belgium, which analyzed approximately 4,000 newborns for 405 genes, also confirmed a disease prevalence of 1.8%, with 0.8% of cases not detectable by existing chemical tests.

Significance and Prospects

Genomic analysis-based newborn screening has the potential to transform the paradigm of clinical medicine by enabling proactive measures to be taken before symptoms appear. The case of Safi Ford, who was diagnosed with a growth hormone deficiency variant in the Generation Study in the United Kingdom and began growth hormone treatment at 6 months of age, clearly demonstrates the benefits of early intervention. Early diagnosis can prevent the time and economic losses that patients would otherwise experience while seeking medical care after the onset of symptoms.

However, there are still many challenges to be addressed before large-scale commercialization can be achieved. The biggest obstacle is the unclear link between gene variants and the actual occurrence of the disease. In infants with a variant in the SCN1A gene, which is associated with epilepsy, the timing and severity of seizures varied completely among patients. This shows that a variant identified through genomic screening does not necessarily guarantee that it will lead to an actual disease.

The psychological distress experienced by parents and the lack of counseling infrastructure are also issues that cannot be ignored. One mother, who was informed that her child had a suspected Smith-Magenis Syndrome (SMS) gene variant, experienced extreme anxiety due to a lack of detailed explanation. Although the variant was eventually found to be benign, the mental anguish caused by inaccurate risk signals is a significant adverse effect. Social consensus must also be established to protect medical data and prevent genetic information from being used for insurance discrimination.