Early Pompe disease treatment means better heart health: Study
Starting ERT in 1st month of life yields better cardiac outcomes, researchers say
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Children with infantile-onset Pompe disease (IOPD) who start enzyme replacement therapy (ERT) within the first month of life have healthier hearts than those who start the treatment later, a study found.
“Our findings support the benefit of early ERT initiation in IOPD, particularly for cardiac outcomes,” the researchers wrote. “The positive effects were consistent across multiple cardiac parameters and analysis approaches, providing robust evidence for early intervention.”
The study, “Early Initiation of Enzyme Replacement Therapy in Infantile Onset Pompe Disease Improves Cardiac Outcomes: A Longitudinal Analysis,” was published in JIMD Reports.
Pompe disease is caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme that helps break down glycogen, a complex sugar. When GAA is missing or not working properly, glycogen builds up — especially in muscle cells — leading to progressive muscle weakness.
In IOPD, Pompe symptoms emerge within the first year of life, and the heart is often severely affected. Cardiomyopathy (heart muscle disease) is common and can be life-threatening if left untreated. ERT, the standard treatment for Pompe, works by providing a functional version of the missing GAA enzyme. This helps to clear glycogen from cells and can improve both muscle and heart health.
Investigating treatment timing
Researchers at Duke University in North Carolina examined how the timing of ERT affected heart outcomes in children with IOPD.
“Although the cardiac system readily responds to ERT, delayed treatment initiation can lead to suboptimal outcomes and incomplete resolution of abnormalities,” they wrote.
The team monitored heart function over time using echocardiograms, which use ultrasound to assess heart structure, and electrocardiograms, which measure the heart’s electrical activity. The study involved 45 children who began ERT after they were one month old and 10 who started treatment within the first month.
The analysis showed that each month of delay in starting ERT was linked to thicker heart muscle walls and a higher left ventricular mass index (LVMI), a measure of heart enlargement. Delays were also associated with changes in the heart’s electrical activity, including longer QRS and QT intervals, which reflect how the heart beats and resets between beats.
Starting treatment later also increased the risk of more serious heart problems, including enlargement of both lower chambers of the heart (biventricular hypertrophy), reduced pumping ability (abnormal ejection fraction and shortening fraction), and a lower chance of reaching a normal LVMI. In fact, the early-treated group achieved a normal LVMI more quickly than the late-treated patients.
Researchers also examined the status of cross-reactive immunologic material (CRIM), which can influence a patient’s response to ERT. In people with Pompe, CRIM status describes whether the body makes any amount of the missing GAA enzyme.
Generally, ERT is less effective in CRIM-negative patients because their bodies don’t make any GAA, so therapeutic GAA can be mistaken for an infectious invader and be attacked by the immune system. In CRIM-positive patients, some GAA is made, which promotes immune tolerance toward therapeutic GAA.
CRIM status alone was not significantly linked to differences in heart measurements. However, among children who were CRIM negative, earlier ERT had an even stronger positive effect on heart measurements including LVMI and heart wall thickness.
“Our study demonstrated that overall, echocardiogram and electrocardiogram parameters appear to have a higher frequency of normal values for age when ERT is initiated earlier,” the researchers wrote.
