Myozyme Benefits LOPD Patient Misdiagnosed For 3 Decades

The woman was seen by four neurologists, underwent two biopsies in 15 years

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A woman was diagnosed with advanced late-onset Pompe disease after three decades of being misdiagnosed, according to a recent case report.

After diagnosis, the woman began treatment with Myozyme (alglucosidase alfa), which led to marked improvements that enabled her to live independently.

The findings underscore a need for clinicians to be more aware of the clinical signs of Pompe and suggest that enzyme replacement therapies (ERT) like Myozyme should be considered for managing advanced LOPD, the researchers said.

The study, “Benefit of 5 years of enzyme replacement therapy in advanced late onset Pompe. A case report of misdiagnosis for three decades with acute respiratory failure at presentation,” was published in Molecular Genetics and Metabolism Reports. 

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Pompe disease is caused by mutations which lead to a deficiency in the acid-alpha glucosidase (GAA) enzyme. As a result, a complex sugar called glycogen builds to toxic levels in cells, especially those in the cardiac and skeletal muscles. Symptoms vary depending on the type of disease-causing mutation and the level of GAA activity in a person’s cells.

Late-onset Pompe, encompassing disease onset in childhood, adolescence, and adulthood, is typically associated with GAA levels less than 30-40% of normal and symptoms that include muscle weakness and shortness of breath that are milder than those seen in infantile-onset Pompe.

LOPD can be difficult to diagnose and misdiagnoses are not infrequent, according to researchers.

The reported case concerned a 57-year-old Caucasian woman who came to the emergency room in Canada reporting progressive muscle weakness, swallowing difficulties (dysphagia), and breathlessness while lying down (orthopnea) that had started six months earlier and worsened significantly in the two weeks before going to the hospital.

The woman said she had muscle weakness in the hip and shoulders since her mid-20s and had been diagnosed with “probable” polymyositis, an inflammatory disease that causes muscle weakness, at 26.

Over the next 15 years, the woman had seen four neurologists and underwent two muscle biopsies due to a lack of a clear diagnosis. Results from the biopsies showed no signs of an inflammatory muscle disease, but no clear diagnosis could be made. A fourth neurologist finally considered Pompe as a possibility.

During the emergency room examination, the woman had weakness in both arms and legs with shortness of breath while seated. Overnight, she began to have respiratory failure with too much carbon dioxide in her bloodstream. Her lung function was severely restricted and electromyography revealed abnormalities in her heart rhythms.

Over the next month, she was treated with noninvasive ventilation in the intensive care unit. During that time, a diagnosis of Pompe disease was confirmed with GAA measurements, which showed severely deficient GAA enzyme activity. A review of her previous muscle biopsies showed a large amount of glycogen accumulation in the muscles.

Genetic analyses confirmed the woman had two disease-causing mutations in the GAA gene, both of which had been previously reported in Pompe patients.

She was discharged from the hospital with profound muscle weakness and was reliant on a wheelchair. One and a half years after her diagnosis, she started using Myozyme, an ERT developed by Sanofi (marketed in the U.S. as Lumizyme) to restore GAA levels.

She remained on Myozyme for five years up to the study’s completion. After two years, her muscle function gradually improved and she was able to walk independently with a cane for up to 500 meters (about 547 yards). She could climb the stairs up to her apartment and was able to live alone.

After more than five years on Myozyme, the woman was still living independently with the use of a cane or walker and continued using respiratory support at night. Over time, her restricted breathing patterns saw a modest improvement and stabilized.

Evidence suggests that “both earlier diagnosis and treatment may be beneficial to patient outcome,” for LOPD patients, the researchers wrote, adding that the findings underscore “the need for more timely diagnosis.”

This issue can be addressed by helping neurologists be better informed about the presentation of Pompe, the researchers suggested, noting that “educational tools from academic and perhaps pharmaceutical companies may also be helpful.”

The findings also add “further weight to recommendations that suggest ‘offering’ ERT to severe LOPD patients,” the research team added, noting that patients should be followed closely to monitor the treatment’s long-term benefits.