Late-onset Pompe disease diagnosed nearly 20 years after symptoms began

A man treated for more than a decade for dermatomyositis, an autoimmune condition that causes muscle weakness and skin rash, was later diagnosed with late-onset Pompe disease (LOPD), according to a U.S. case report. He was 52 when he first visited the reporting clinic.

Despite treatment with several immunosuppressive medications, his muscle weakness continued to worsen. After his sister was diagnosed with Pompe disease, clinicians pursued further testing that confirmed he had the condition, nearly 20 years after his symptoms first appeared. He subsequently began enzyme replacement therapy (ERT) for Pompe.

“The diagnosis of LOPD is a clinical challenge and often delayed by years from symptom onset,” the researchers wrote.

The case, “Of Pompe and Circumstance: A Case Review of Late Onset Pompe Disease in a 52-Year-Old Male,” was published in the journal Case Reports in Rheumatology.

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Pompe disease can resemble inflammatory muscle conditions

Pompe disease is caused by mutations in the GAA gene, which contains instructions for making an enzyme called acid alpha-glucosidase (GAA). This enzyme breaks down glycogen, the body’s stored form of sugar.

When GAA activity is insufficient, glycogen builds up inside cells, particularly muscle cells, causing progressive muscle damage and weakness. LOPD symptoms can begin in childhood or adulthood. They typically include weakness in muscles near the center of the body and breathing difficulties.

These symptoms can resemble those of inflammatory muscle diseases, including dermatomyositis. However, the conditions require different treatments. Dermatomyositis is generally treated with medications that suppress the immune system, while Pompe disease is typically treated with ERT.

The California researchers used this case to highlight how difficult it can be to distinguish LOPD from inflammatory muscle diseases. They also emphasized the importance of reconsidering a diagnosis when a patient’s condition continues to worsen despite treatment.

The patient, originally from Egypt, began experiencing weakness in his arms, legs, and neck at age 37. He also developed rashes on his hands and elbows.

At age 41, he was diagnosed with dermatomyositis after undergoing electrical testing of muscle activity and a muscle biopsy. However, the researchers could not obtain the original test reports.

Over the years, he received several treatments, including the immunosuppressive medications methotrexate, azathioprine, and rituximab, as well as the steroid prednisone. He also received intravenous immunoglobulin (IVIG), a treatment made from antibodies collected from donated human plasma that helps regulate immune-system activity.

Muscle weakness persisted despite years of treatment

At 52, he visited the researchers’ clinic because he continued to have widespread muscle weakness and difficulty walking. An examination showed weakness in his arms, legs, and neck. He also had foot drop in both feet, which can cause the toes to drag while walking, and needed support to rise from a chair.

Despite these symptoms, blood tests measuring muscle injury and inflammation were largely normal, as were tests for antibodies associated with inflammatory muscle diseases.

The clinicians initially thought his weakness was due to residual muscle damage, physical deconditioning (a consequence of inactivity), and possibly low-level inflammation. A CT scan later showed muscle wasting and fatty buildup in muscles of the chest and back.

Four years later, the patient reported that his sister had been diagnosed with LOPD, prompting doctors to investigate whether he had the same condition.

Testing revealed reduced GAA enzyme activity and disease-causing variants in the GAA gene, confirming Pompe disease. An MRI scan also showed extensive muscle wasting in his hips and thighs without signs of active inflammation.

The patient subsequently began ERT with Nexviazyme (avalglucosidase alfa), with the goal of preventing his muscle weakness from worsening. The report did not provide follow-up results describing his response to treatment.

“This case highlights the challenges of inheriting a patient with a chronic diagnosis from a different health network, discontinuing long-time treatments, and the difficult conversations of calling a long-time diagnosis into question and requesting additional specialized testing and treatment,” the team concluded. “It underscores the importance of obtaining detailed medical records, regular patient follow-up and continuity, and the need for confirmatory or repeat testing in the presence of diagnostic uncertainty.”