Early ERT is key to better outcomes in the Pompeii study in children | The Pompe neonatal screening enables an important early intervention with ERT


Enzyme replacement therapy (ERT) given as soon as possible may lead to better outcomes in affected children Classic Pompe disease in children (IOPD), according to a long-term study conducted in Taiwan.

“Our study demonstrates that administration of vaccination therapy as early as possible and use of short-term hydrocortisone anesthesia leads to better long-term outcomes,” the researchers say.

the study, “Long-term outcomes of very early childhood Pompe disease treated with short-term steroid anaesthesia: trials from a nationwide newborn screening program“in Journal of Medical Genetics.

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Pompe disease is caused by mutations In the GAA The gene that leads to alpha-glucosidase (GAA) deficiency. This enzyme is responsible for breaking down a complex sugar molecule called glycogen. As a result, glycogen accumulates to toxic levels in cells, especially those in cardiac and skeletal muscles.

IOPD is the most severe form of this disease. In classic IOPD, symptoms They appear during the first few months of life.

Museum, developed by Sanofi Genzyme (Marketed in the United States as Lumizim), the first approved ERT for Pompe disease, and designed to administer a working version of the GAA enzyme.

Previous studies have shown that reparative therapy can improve motor skills, heart function, and patients’ survival. However, outcomes in IOPD depend on when treatment is given, with weaker responses likely to occur when muscle damage is already severe and irreversible.

In this long-term follow-up study, a team led by researchers at Taipei Veterans General Hospital, in Taiwan, analyzed the outcomes of IOPD patients who received early ERT and compared them to patients from other medical centers. The steroid hydrocortisone, as a pre-treatment, has been used to reduce muscle inflammation and prevent immune responses against ERT.

The hospital established a newborn screening program for Pompeii in 2008

The center established a newborn screening program for Pompe disease in 2008, with the Rapid Diagnostic Criteria for IOPD established two years later. Newborn screening uses a small blood sample collected shortly after birth to look for GAA enzyme activity. When low GAA activity is confirmed, another blood sample is analyzed to confirm the initial diagnosis.

Over an 11-year period (January 2010 to February 2021), 1,228,539 newborns were screened for Pompe disease, resulting in 33 with confirmed IOPD. A total of 26 newborns received first aid treatment within six hours of their first admission and were followed up over an average of six years.

The treatment protocol first included intravenous administration of hydrocortisone at a dose of 2 mg/kg. Then Myozyme followed. Hydrocortisone was tapered off three months after the first ERT infusion. ERT was given every 2 weeks but was given more often or in higher doses if the patient’s clinical symptoms deteriorated.

During follow-up, a comprehensive blood test was performed every three to six months. Pulmonary function was assessed starting at 3 years of age, and hearing and vision were assessed at least once annually. Also, patients’ developmental outcomes were assessed once or twice a year using the Bayley Scale of Infant and Toddler Development, Second Edition.

Patients with classic IOPD started ERT with a mean age of 9.75 days. When including those with non-classical IOPD, treatment was started with a mean of 11.18 days.

All patients survived without the need for artificial respiration and near-normal respiratory function, according to the researchers. All children also had normal heart volumes and cognitive functions, and they reached motor milestones within the expected time. Their body weight and height were also normal for their age.

The team then compared their patients’ results to those described in nine studies. Two of the studies were conducted in Taiwan, while the remaining seven studies were conducted in the United States or Europe. The researchers noted that most patients in the US and European studies were diagnosed based on clinical signs and symptoms, rather than through newborn screening programmes. When compared to the Taiwanese studies, clinical outcomes were worse and treatment was started late in the other studies.

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“Our patients had better clinical outcomes,” the researchers wrote when comparing outcomes for patients at Taipei Veterans’ Hospital with a group from a different center in Taiwan. They attributed this to the early administration of ERT combined with hydrocortisone sedation.

Overall, patients who followed this early regimen achieved independent walking at a younger age (11.9 months vs. 15.15 months) and better (highest) cognitive scores on the Bayley Scale, with a mean score of 105.0 vs. 82. Within two years of ERT, the children had Also lower levels of creatine kinase, a marker of muscle damage, and lower levels of antibodies against ERT.

The researchers concluded, “Using ERT very early with our rapid diagnosis and treatment strategy enabled our patients with IOPD to achieve better outcomes than patients at other medical centers.”


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