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. 2024 Jan 8:11:1221140.
doi: 10.3389/fped.2023.1221140. eCollection 2023.

An analysis of Pompe newborn screening data: a new prevalence at birth, insight and discussion

Ryan Colburn  1 , David Lapidus  2
Affiliations

An analysis of Pompe newborn screening data: a new prevalence at birth, insight and discussion

Ryan Colburn et al. Front Pediatr. .

Abstract

This study includes over 11.6M newborns screened (NBS) for Pompe Disease (PD) from 29 distinct universal screening programs across 8 countries and 4 continents. The birth prevalence of PD is 1:18,711, with no evidence of difference across populations of European, Latin American, or Asian ancestry, though differences may exist for PD subtypes. This study also compares these results, based on direct detection of disease and analyzed using a binomial method along with power analysis, with other methods for estimating the 'frequency' of rare genetic diseases (such as utilizing Hardy-Weinberg equilibrium on allele frequency and confidence interval analysis). This comparison demonstrates the implications of sample size and frames a discussion on its influence on the reliability of results when extrapolating to a population beyond the study dataset.

Objectives: Primary: Establish a new figure for prevalence at birth for Pompe disease by collecting and analyzing the largest relevant dataset to date and using that result to project population prevalence at birth in a novel way. Secondary: Compare these results to previous analyses to offer a framework for evaluating 'frequency' data that can be applied to other rare, genetic diseases, along with methods to assess quality of estimates.

Keywords: Pompe (glycogen storage disease type 2/II); autosomal recessive inheritance; diagnosis/diagnostic yield; genetic prevalence; gnomAD; lysosomal storage disorder/disease (LSD); newborn screening (NBS); rare disease epidemiology.

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Conflict of interest statement

RC was employed by odimm inc., DL was employed by LapidusData Inc. The Rare Crossroads fund for community led Initiatives in Pompe is managed by RC and has received contributions from M6P Therapeutics, Askbio, Astellas Gene Therapies, Maze Therapeutics, and contributors from the Pompe community.

Figures

Figure 1
Figure 1
Generalized Pompe diagnosis via NBS process flow.
Figure 2
Figure 2
Generalized example of sources of variability in NBS based prevalence estimates.
Figure 3
Figure 3
Pompe birth prevalence by state/country and by Region with 95% CI.
Figure 4
Figure 4
Pompe birth prevalence by state/country with 95% CI, and cumulative rate ordered by newborns screened (increasing sample size).
Figure 5
Figure 5
Pompe birth prevalence vs. newborns screened by state/country.
Figure 6
Figure 6
IOPD birth prevalence vs. newborns screened by state/country.
Figure 7
Figure 7
LOPD birth prevalence vs. newborns screened by state/country.
Figure 8
Figure 8
Pompe birth prevalence vs. total newborns screened by region
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See this image and copyright information in PMC

References

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