Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme

Abstract

BackgroundStarting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres.MethodsIn this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups.ResultsThe average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects.ConclusionVery early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.

The Importance of Early Treatment of Inherited Neuromuscular Conditions

“…Of the Taiwanese CRIM-positive IOPD cohort, 26 patients were followed for an average of 6.18±3.14 years. All patients included in the study had normal heart sizes, achieved typical motor milestones, demonstrated intact cognitive function, and displayed pulmonary function that ranged from near-normal to normal [ 145 ]. Long-term study in one of the largest cohort of IOPD in France recently showed fewer benefits of ERT, with only temporary improvements followed by muscle and respiratory function deterioration; however, the impact of the age of ERT initiation was not explicitly assessed [ 146 ].∥Real-world data in patients who were either pre-symptomatic or lacked clinical or chemical signs of deterioration demonstrate the benefit of higher doses of ERT (e.g., 40 mg/kg every other week and 20 mg/kg weekly) early in life [ 147, 148 ].…”

“…Cipalglucosidase alfa (Pombiliti ® ) is another ERT, used in combination with miglustat [108]. Avalglucosidase alfa was shown to be a safe and efficient alternative to alglucosidase alfa in LOPD [109][110][111] and has received marketing authorization in several countries for LOPD and/or IOPD, whereas cipaglucosidase alfa has received recent approval for adult LOPD [145]. Results from the mini-COMET trial suggest that avalglucosidase alfa is beneficial in IOPD patients who are less than 18 years of age who were declining on alglucosidase alfa [112], but the timing of treatment was not specifically evaluated.…”

Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy

“…Enzyme analyses on leukocytes/lymphocytes, biochemical assays demonstrating accumulation and gene analyses can confirm the clinical diagnosis [ 5 , 6 ]. The treatment (enzyme-replacement therapy ERT, hematopoietic stem-cell transplantation HSCT, chaperones and gene therapy) can significantly improve outcomes, but the progressive nature of these diseases makes early diagnosis essential [ 7 , 8 , 9 , 10 ].…”