Early clinical phenotype of late onset Pompe disease: Lessons learned from newborn screening

Mol Genet Metab. 2022 Mar;135(3):179-185. doi: 10.1016/j.ymgme.2022.01.003.

PMID: 35123877

Erin Huggins, Maggie Holland, Laura E Case

Highlights: Careful physical therapy evaluation is necessary to monitor for subtle musculoskeletal signs that may reflect early muscle involvement in late onset Pompe disease patients.

Abstract

Purpose: To offer guidelines for long-term follow-up, thoroughly phenotype children with late-onset Pompe disease (LOPD) detected via newborn screening (NBS).

Methods: Twenty infants diagnosed with LOPD by NBS between the ages of 6 and 21 months completed a comprehensive clinical examination at Duke University, which included cardiac imaging, biomarker testing, physical therapy evaluation, and speech-language pathology evaluation.

Results: Four of the 20 newborns were homozygous for the "late-onset" IVS1 splice site variant c.-32-13 T > G, fourteen were compound heterozygous, and two had no copies. There was no evidence of cardiomyopathy or heart rhythm abnormalities in any of the patients. In eight patients (40%), biomarker testing revealed an increase in CK, AST, and ALT, as well as an elevation in Glc4 in two individuals (10%). All of the patients had postural and kinematic issues. On the Alberta Infant Motor Scale (AIMS), three patients (17%) scored below the 10 percentile, whereas 15 patients (83%) scored above the 10 percentile. All patients' speech-language pathology evaluations were normal, and nine individuals had mild feeding/swallowing difficulties (45%).

Conclusion: The findings of this study reveal that children with LOPD diagnosed using NBS have a wide range of symptoms. To keep an eye out for subtle musculoskeletal symptoms that could indicate early muscle involvement, a thorough physical therapy evaluation is required. The progression of symptoms should be closely monitored.

Keywords: Late-onset Pompe disease, Newborn screening, Pompe disease