Newborn Screening for 6 Lysosomal Storage Disorders in China
Siyu Chang1, Xia Zhan1, Yuchao Liu1
1Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Newborn screening in Shanghai found a high birth prevalence of lysosomal storage disorders (LSDs). Tandem mass spectrometry (MS/MS) identified 27 newborns with LSDs, predominantly later-onset forms.
Area of Science:
- Genetics and Genomics
- Public Health
- Biochemistry
Background:
- Newborn screening (NBS) for lysosomal storage disorders (LSDs) is crucial for early detection and management.
- Limited data exists on the birth prevalence and subclinical forms of LSDs in the Chinese population.
- Evaluating NBS for LSDs in Shanghai addresses a critical public health knowledge gap.
Purpose of the Study:
- To determine the birth prevalence of six specific LSDs in the Shanghai newborn population.
- To characterize subclinical forms of LSDs using clinical, biochemical, and genetic analyses.
- To assess the utility of tandem mass spectrometry (MS/MS) in NBS for LSDs.
Main Methods:
- A cohort of 50,108 newborns in Shanghai were screened for Gaucher, ASMD, Krabbe, MPS I, Fabry, and Pompe diseases using MS/MS.
- Screen-positive newborns underwent confirmatory molecular, biochemical, and clinical evaluations.
- Data analysis spanned January 2021 to October 2022.
Main Results:
- The combined birth prevalence of the six LSDs was 1 in 1856 live births.
- Krabbe disease (1/5568), Fabry disease (1/6264), and ASMD (1/10,022) were the most prevalent.
- Of the 27 diagnosed newborns, 11.1% had early-onset forms, while 88.9% presented with later-onset forms.
Conclusions:
- The birth prevalence of these six LSDs in Shanghai is notably high.
- MS/MS-based NBS effectively identifies and characterizes newborns with LSDs.
- Findings support improved parental counseling and management strategies for LSDs.
Importance:
Newborn screening (NBS) for lysosomal storage disorders (LSDs) is becoming an increasing concern in public health. However, the birth prevalence of these disorders is rarely reported in the Chinese population, and subclinical forms of diseases among patients identified by NBS have not been evaluated.
Objective:
To evaluate the birth prevalence of the 6 LSDs in the Shanghai population and determine subclinical forms based on clinical, biochemical, and genetic characteristics.
Design, Setting, And Participants:
This cohort study included 50 108 newborns recruited from 41 hospitals in Shanghai between January and December 2021 who were screened for 6 LSDs using tandem mass spectrometry (MS/MS). Participants with screen-positive results underwent molecular and biochemical tests and clinical assessments. Data were analyzed from January 2021 through October 2022.
Exposures:
All 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 353 newborns who were positive. Of these, 27 newborns (7.7%) were diagnosed with 1 of 6 LSDs screened, including 2 newborns with Gaucher, 5 newborns with ASMD, 9 newborns with Krabbe, 8 newborns with Fabry, and 3 newborns with Pompe disease. The combined birth prevalence of LSDs in 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 clinical forms accounted for 3 newborns with positive results (11.1%), while later-onset forms represented nearly 90% of diagnoses (24 newborns [88.9%]).
Conclusions And Relevance:
In this study, the combined birth prevalence of the 6 LSDs in Shanghai was remarkably high. MS/MS-based newborn screening, combined with biochemical and molecular genetic analysis, successfully identified and characterized newborns who were screen-positive, which may assist with parental counseling and management decisions.
