Outcome of Later-Onset Pompe Disease Identified Through Newborn Screening.

OBJECTIVE: To determine the outcomes of patients with later-onset Pompe disease (LOPD) identified through newborn screening (NBS). STUDY DESIGN: A prospective observational cohort study was conducted from the initiation of Pompe disease NBS by following subjects every 3-12 months for motor development and biochemical markers. RESULTS: Between 2005 and 2018, 39 of 994 975 newborns evaluated were classified as having LOPD based on low acid α-glucosidase (GAA) activity but no cardiac involvement at the time of screening. As of December 2020, 8 of these 39 infants (21%) were treated with enzyme replacement therapy owing to persistent elevation of creatine kinase (CK), cardiac involvement, or developmental delay. All subjects' physical performance and endurance improved after treatment. Subjects carrying c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] presented a phenotype of nonprogressive hypotonia, muscle weakness, and impairment in physical fitness tests, but they have not received treatment. CONCLUSIONS: One-fifth of subjects identified through NBS as having LOPD developed symptoms after a follow-up of up to 15 years. NBS was found to facilitate the early detection and early treatment of those subjects. GAA variants c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] might not cause Pompe disease but still may affect skeletal muscle function.

Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth.

OBJECTIVE: To determine the benefit of newborn screening for the long-term prognosis of patients with classic infantile-onset Pompe disease (IOPD). STUDY DESIGN: A cohort of patients with classic IOPD were diagnosed by newborn screening, treated with recombinant human acid α-glucosidase (rhGAA), and followed prospectively. Outcome measurements included survival, left ventricular mass, serum creatinine kinase, motor function, mental development, and systemic manifestations. RESULTS: Ten patients who presented with left ventricular hypertrophy at diagnosis received rhGAA infusions starting at a median age of 16 days (6-34 days). All patients were cross-reactive immunologic material-positive. After a median treatment time of 63 months (range 28-90 months), all could walk independently, and none required mechanical ventilation. All patients had motor capability sufficient for participating in daily activities, but muscle weakness over the pelvic girdle appeared gradually after 2 years of age. Ptosis was present in one-half of the patients, and speech disorders were common. Anti-rhGAA antibody titers were low (median maximal titer value 1:1600, range: undetectable ∼ 1:12,800). CONCLUSION: By studying patients treated since birth who have no significant anti-rhGAA antibody interference, this prospective study demonstrates that the efficacy of rhGAA therapy is high and consistent for the treatment of classic IOPD. This study also exposes limitations of rhGAA treatment. The etiology of the manifestations in these early-treated patients will require further study.

Later-onset Pompe disease: early detection and early treatment initiation enabled by newborn screening.

OBJECTIVE: To determine whether newborn screening facilitates early detection and thereby early treatment initiation for later-onset Pompe disease. STUDY DESIGN: We have conducted a newborn screening program since 2005. Newborns with deficient skin fibroblast acid α-glucosidase activity and two acid α-glucosidase gene mutations but no cardiomyopathy were defined as having later-onset Pompe disease, and their motor development and serum creatine kinase levels were monitored every 3 to 6 months. RESULTS: Among 344 056 newborns, 13 (1 in 26 466) were found to have later-onset Pompe disease. During a follow-up period of up to 4 years, four patients were treated because of hypotonia, muscle weakness, delayed developmental milestones/motor skills, or elevated creatine kinase levels starting at the ages of 1.5, 14, 34, and 36 months, respectively. Muscle biopsy specimens obtained from the treated patients revealed increased storage of glycogen and lipids. CONCLUSION: Newborn screening was found to facilitate the early detection of later-onset Pompe disease. A subsequent symptomatic approach then identifies patients who need early treatment initiation.