Newborn Screening for 6 Lysosomal Storage Disorders in China

IMPORTANCENewborn screening (NBS) for lysosomal storage disorders (LSDs) is becoming anincreasing concern in public health. However, the birth prevalence of these disorders is rarelyreported in the Chinese population, and subclinical forms of diseases among patients identified byNBS have not been evaluated. OBJECTIVETo evaluate the birth prevalence of the 6 LSDs in the Shanghai population anddetermine subclinical forms based on clinical, biochemical, and genetic characteristics. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 50 108 newborns recruitedfrom 41 hospitals in Shanghai between January and December 2021 who were screened for 6 LSDsusing tandem mass spectrometry (MS/MS). Participants with screen-positive results underwentmolecular and biochemical tests and clinical assessments. Data were analyzed from January 2021through October 2022. EXPOSURESAll participants were screened for Gaucher, acid sphingomyelinase deficiency (ASMD),Krabbe, mucopolysaccharidosis type I, Fabry, and Pompe diseases using dried blood spots. MAIN OUTCOMES AND MEASURES Primary outcomes were the birth prevalence and subclinical forms of the 6 LSDs in the Shanghai population. Disease biomarker measurements, genetic testing, and clinical analysis were used to assess clinical forms of LSDs screened. RESULTS Among 50 108 newborns (26 036 male [52.0%]; mean [SD] gestational age, 38.8 [1.6]weeks), the mean (SD) birth weight was 3257 (487) g. The MS/MS-based NBS identified 353newborns who were positive. Of these, 27 newborns (7.7%) were diagnosed with 1 of 6 LSDsscreened, including 2 newborns with Gaucher, 5 newborns with ASMD, 9 newborns with Krabbe, 8newborns with Fabry, and 3 newborns with Pompe disease. The combined birth prevalence of LSDsin Shanghai was 1 diagnosis in 1856 live births, with Krabbe disease the most common (1 diagnosis/5568 live births), followed by Fabry disease (1 diagnosis/6264 live births), and ASMD (1 diagnosis/10 022 live births). Biochemical, molecular, and clinical analysis showed that early-onset clinicalforms accounted for 3 newborns with positive results (11.1%), while later-onset forms representednearly 90% of diagnoses (24 newborns [88.9%]). CONCLUSIONS AND RELEVANCEIn this study, the combined birth prevalence of the 6 LSDs inShanghai was remarkably high. MS/MS-based newborn screening, combined with biochemical andmolecular genetic analysis, successfully identified and characterized newborns who were screen-positive, which may assist with parental counseling and management decisions