Effect of Newborn Genomic Screening for Lysosomal Storage Disorders: A Randomized Clinical Trial in China

Abstract Background Lysosomal storage disorders (LSDs) have a relatively high incidence among rare diseases and can lead to severe consequences if not treated promptly. However, many countries and regions have not included these disorders in their newborn screening programs, resulting in missed early detection, underdiagnosis, and delayed treatment. Newborn genomic screening has shown good screening effectiveness for traditional biochemical screening diseases; however, its effectiveness for LSDs has not yet been evaluated in the general newborn population. Methods To evaluate the outcome of newborn genomic screening for LSDs, a cohort study was conducted involving newborns recruited from Nanjing Women and Children’s Healthcare Hospital in China from March 18, 2022, to September 21, 2023. All participants underwent genomic screening of 15 LSDs (18 genes) via dried blood spots, with enzyme activity testing of positive samples. The study calculated the prevalence and carrier rates for each LSD, as well as the positive screening rate, the false positive rate and the positive predictive value of the screening process. Results This study prospectively recruited 22,687 newborns (11,996 males [52.88%]). The mean (SD) gestational week was 39.2 (1.08) weeks, and the mean (SD) birth weight was 3369.7 (412.95) g. Genomic screening identified 1,344 carriers (6.0%) and 30 (0.13%) initial positive newborns for LSDs. Among the 30 initial positive newborns, 4 were excluded, 15 newborns were diagnosed, and 11 newborns were followed-up. The combined birth incidence of LSDs in Nanjing, Jiangsu Province, is 1/1,512, mainly Fabry disease, Krabbe disease, glycogen storage disease type II, Niemann-Pick disease and mucopolysaccharidosis type II. Compared with enzyme activity detection, newborn genomic screening had greater positive predictive value (P < 0.05) and a lower false positive rate (P < 0.05). Conclusions This study emphasizes the clinical utility of incorporating newborn genomic screening for LSDs into routine newborn screening, offering a proactive approach for early detection and intervention, ultimately enhancing public health and the well-being of newborns and their families.