Newborn screening for Pompe disease helps avoid years of treatment delay
Testing at birth identifies children who need ERT long before symptoms show
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Newborn screening is uncovering signs of Pompe disease in infants months or even years before obvious symptoms appear, allowing for early treatment that can normalize markers of muscle damage, according to new research.
A study tracking seven children with late-onset Pompe disease (LOPD) found that starting enzyme replacement therapy (ERT) in infancy led to significant improvements in motor function and physical development.
Researchers noted that these cases offer evidence that the “late-onset” label may be a misnomer for many children. By identifying these cases at birth, doctors can intervene before muscle weakness becomes permanent.
Overall, “these cases provide further evidence to support the utility of early diagnosis of LOPD facilitated by [newborn screening], leading to identification of children with early symptom presentation that may benefit from initiation of ERT,” researchers wrote.
The study, “Early enzyme replacement therapy in late-onset Pompe disease diagnosed by newborn screening,” was published in Molecular Genetics and Metabolism.
The challenge of hidden symptoms
Pompe disease is caused by mutations in the GAA gene, which encodes the enzyme acid alpha-glucosidase (GAA) that breaks down glycogen. Without sufficient functional GAA, sugar molecules accumulate and damage cells throughout the body. In LOPD, symptoms typically emerge after the first year of life, but the timeline is highly unpredictable.
A specific mutation, c.-32-13T>G (also known as IVS1), is frequently associated with LOPD, yet patients with this mutation exhibit widely varying symptoms. This often leads to “diagnostic odysseys” where children go a decade or more without a correct diagnosis. Newborn screening is now closing that gap, detecting the disease before parents notice the first symptom.
The study, led by a team at Duke University, followed seven children diagnosed via NBS from 2016 to 2024. These infants started ERT at a median age of 8.2 months. While ERT is the mainstay of treatment for stabilizing muscle and breathing function, there has been an ongoing debate about exactly when to start treatment in children who appear “healthy” at birth.
All children had the IVS1 mutation plus a second mutation that was severe in six cases. The median age at ERT initiation was 8.2 months (range 2-20 months).
The children in this study initially received Lumizyme (alglucosidase alfa) and eventually transitioned to Nexviazyme (avalglucosidase alfa). Before starting therapy, all seven children already showed subtle movement and posture patterns consistent with early muscle weakness. Lumizyme and Nexviazyme are marketed by Sanofi, which co-funded the study with Amicus Therapeutics.
Once treatment began, kinematic deficits, or specific movement errors, decreased in every child. Standardized testing confirmed that while six of the seven children started therapy with motor scores at or below the 10th percentile, they all showed steady acquisition of new physical skills after beginning ERT.
The therapy also affected internal markers of health. All children were born with elevated levels of creatine kinase (CK), a telltale sign of active muscle damage. In every case, CK levels normalized within a median of 6.5 months after starting ERT and remained stable thereafter.
Despite the motor gains, the researchers highlighted that LOPD is a complex condition that requires more than just medication. Several children were diagnosed with mild speech or language disorders, and five showed signs of oral motor impairment or difficulty swallowing (dysphagia).
“Data presented here supports existing evidence that infants and children with LOPD can present with early symptom onset,” the investigators concluded. They emphasized that a comprehensive, multidisciplinary evaluation is essential for children diagnosed through NBS to ensure that every facet of the disease is addressed as early as possible.
