Genotype-phenotype correlation and CRIM status in Vietnamese children with Pompe disease: a single-center experience.

BACKGROUND

Pompe disease (PD) is a rare autosomal recessive disorder caused by pathogenic variants in the 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 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.