Myozyme shows limited efficacy in late-diagnosed woman: Report
Case highlights difficulties in treating Pompe, especially when diagnosed late
Myozyme (alglucosidase alfa), sold as Lumizyme in the U.S., eased breathing but did not improve motor function of the arms and legs in an Iranian woman with late-onset Pompe disease who went undiagnosed for many years, according to a case report.
The researchers say this case highlights the difficulties of treating Pompe disease, particularly when it’s diagnosed late. Despite the use of Myozyme, this patient — who was diagnosed about two decades after symptom onset — still needed a ventilator two years after starting treatment.
“Timely diagnosis of Pompe disease is paramount for its effective management and improved [patient] outcomes,” the researchers wrote. “It is important to note that treatment during advanced stages of the disease may not yield substantial benefits.”
The report was titled “Significance of early diagnosis and treatment of adult late-onset Pompe disease on the effectiveness of enzyme replacement therapy in improving muscle strength and respiratory function: a case report” and published in the Journal of Medical Case Reports.
Symptoms began at 16, but patient not diagnosed until age 38
In Pompe disease, mutations in the GAA gene result in low to no activity of acid alpha-glucosidase, an enzyme needed to break down a sugar called glycogen. Too much glycogen is toxic, particularly to muscle cells, which use the sugar as a source of energy. As a result, patients develop progressive muscle weakness and other disease symptoms.
Enzyme replacement therapy (ERT) — such as Myzoyme/Lumizyme — can ease symptoms of Pompe disease by providing the body with the enzyme it needs to break down glycogen. However, treatment started in the later stages of the disease may not be as effective as if it’s started early.
Here, the researchers described the case of a 38-year-old Iranian woman who was diagnosed with Pompe disease about 20 years after the onset of symptoms. By the time she was started on treatment, she had been bedridden and ventilator-dependent for 12 years.
The woman had begun experiencing muscle weakness at age 16, which worsened after a miscarriage at age 19. Over time, she developed difficulty breathing and was placed on a ventilator. She did not respond to treatment with corticosteroids and azathioprine, an immunosuppressive medication.
After giving birth at age 23, the woman sought treatment at a hospital for shortness of breath and muscle weakness. Her still-undefined condition had progressed “such that she could no longer get up or walk without assistance,” the researchers wrote. After staying for about two years in the hospital, the woman was discharged home without a definite diagnosis.
For 12 years, she remained on a ventilator at home. “Later, the patient was referred to us,” the researchers wrote, noting that the team tested her for Pompe disease at age 36.
A blood test revealed low alpha-glucosidase activity, and a genetic test confirmed the presence of disease-causing mutations.
Myozyme was started at a dose of 20 mg/kg every two weeks. After two years on the ERT, the woman had experienced slight improvement in breathing. However, she remained bedridden and dependent on a ventilator. Her muscle strength improved slightly in the limbs.
Early intervention … plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients.
Chest CT scans before and after Myozyme treatment revealed a buildup of fluid in and around the lungs. This was likely caused by being immobile for a long time and experiencing repeated aspirations (involving the inhaling food or liquids), the team noted.
The researchers concluded that, while ERT can ease some symptoms, problems like an unstable enzyme and difficulty delivering it to muscle cells may limit how well treatment works, especially in the advanced stages of Pompe disease.
“Early intervention … plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients,” the researchers wrote.
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