High prevalence of GAA c.[752C>T;761C>T] haplotype complicates high-risk screening for Pompe disease in the Chinese population

GAA c.[752C>T;761C>T] haplotype as pseudodeficiency allele causing false-positive screening results in East Asian populations

A retrospective review of the Chinese Pompe disease high-risk screening program identified 22 individuals from 11 independent families carrying the GAA c.[752C>T;761C>T] haplotype. Disease occurred only when the haplotype was coupled with two pathogenic variants in trans, while homozygous individuals or those with a single pathogenic variant remained asymptomatic despite GAA activity below the diagnostic threshold. This haplotype is enriched in East Asian populations (allele frequencies ~0.26%) and must be systematically recognized as a pseudodeficiency allele to avoid unjustified enzyme replacement therapy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This work is directly applicable to laboratories performing Pompe disease screening in East Asian populations and their diaspora. The 0.26% allele frequency represents a significant source of false positives. An important message for screening laboratories in France, where these populations are represented.