Outcome of Later-Onset Pompe Disease Identified Through Newborn Screening

J Pediatr. 2022 Jan 4;S0022-3476(21)01279-8. doi: 10.1016/j.jpeds.2021.12.072.

PMID: 34995642

Ni-Chung Lee, Kai-Ling Chang, Stijn L M In 't Groen

Highlights: The aim of this study was to determine the outcomes of patients with later-onset Pompe disease (LOPD) identified through newborn screening (NBS).

Abstract

Objective: The goal of this study was to determine the outcomes of patients with later-onset Pompe disease (LOPD) who were identified by newborn screening (NBS).

Study design: From the start of the NBS for Pompe disease, individuals were followed every 3-12 months for motor development and biochemical markers in a prospective observational cohort research.

Results: Based on low acid-glucosidase (GAA) activity but no cardiac dysfunction at the time of screening, 39 of 994 975 newborns were diagnosed with LOPD between 2005 and 2018. Because of chronic elevations of creatine kinase (CK), cardiac involvement, or developmental delay, 8 of these 39 infants (21%) were treated with enzyme replacement therapy as of December 2020. After therapy, all of the individuals' physical performance and endurance improved. Subjects with the mutations c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] had nonprogressive hypotonia, muscle weakness, and impairment in physical fitness tests, but they were not treated.

Conclusions: After a 15-year follow-up, one-fifth of the participants diagnosed with LOPD using NBS exhibited symptoms. NBS was discovered to aid in the early detection and treatment of those individuals. Although the GAA variants c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] are unlikely to cause Pompe disease, they may have an impact on skeletal muscle function.

Keywords: enzyme replacement therapy, genetic variations, glycogen storage disease type II, hypotonia, manifestation–neuromuscular