Abstract
BACKGROUND: Pompe disease (PD) is a rare autosomal recessive disorder caused by pathogenic variants in the GAA gene, resulting in deficient lysosomal acid α-glucosidase activity. Clinical manifestations range from classic infantile-onset (IOPD) to late-onset (LOPD) phenotypes. Understanding genotype-phenotype correlations in PD is essential for prognosis and individualized therapy. METHODS: This retrospective, single-center study included 26 Vietnamese pediatric patients diagnosed with PD. Clinical, biochemical, and genetic data were systematically collected. Genotype-phenotype correlation, CRIM status distribution, and survival outcomes were analyzed. RESULTS: Of 26 patients, 23 had IOPD and 3 had LOPD. CRIM-positive status was identified in 87.0% of IOPD and 33.3% of LOPD patients. The most frequent variants were c.1843G > A and c.1933G > C. Two previously unreported variants (c.2016del, c.1723T > C) were detected. Hypertrophic cardiomyopathy and hypotonia were universal among IOPD cases. Despite ERT administration in 52.9% of patients, overall mortality in the infantile group was 60.8%. Variant pathogenicity correlated with both CRIM status and clinical outcomes. CONCLUSION: These findings underscore the clinical importance of comprehensive GAA genotyping and CRIM status determination in predicting disease course and guiding therapeutic decisions. Our results further emphasize the need for population-specific variant databases to inform newborn screening and precision treatment initiatives across Southeast Asia.