Breathing problems, muscle weakness lead to LOPD diagnosis
Study: Woman's case highlights challenges of confirming disease
A 43-year-old woman who was experiencing breathing problems and muscle weakness was eventually diagnosed with late-onset Pompe disease (LOPD) through genetic testing, highlighting the challenges of diagnosing the condition due to its rarity and nonspecific symptoms, according to a study.
“It is important to consider late-onset Pompe disease in adults presenting with unexplained respiratory insufficiency and progressive muscle weakness,” clinicians wrote.
Case details were presented in the study “Unexplained Progressive Respiratory Insufficiency and Weakness Diagnosed as Late-Onset Pompe Disease Through Biochemical and Molecular Genetic Testing,” published in The Neurohospitalist.
Woman admitted to ICU with multiple symptoms
In Pompe, mutations in the GAA gene cause a deficiency in the enzyme acid alpha-glucosidase, which leads to the buildup of the complex sugar glycogen in muscles. Typical manifestations include poor muscle tone, progressive muscle weakness, fatigue, hearing impairment, eating issues, breathing problems, and frequent respiratory infections.
A diagnosis of LOPD, which is characterized by symptoms emerging any time after the first year of life, is often challenging because of its rarity, slow progression, and nonspecific symptoms.
In this report, a team led by clinicians at the Vanderbilt University Medical Center in Tennessee described the case of an African American woman who was admitted to the intensive care unit with progressive weakness, respiratory failure, and altered consciousness.
Nine months before the admission, she was hospitalized for two weeks for breathing problems and aspiration pneumonia, a type of pneumonia caused by inhaling food or liquid into the lungs. After that, she experienced persistent shortness of breath and was started on supplemental oxygen therapy at home. One day before admission, she developed garbled speech and confusion. By the next morning, she had became increasingly confused.
Biochemical, molecular genetic testing crucial, clinicians say
Although she was alert when she arrived at the emergency department, she appeared ill, with a low body temperature and a fast heart rate. While on oxygen, her breathing rate and blood oxygen levels were within the normal range, though she was nonverbal and unable to follow commands.
She had strength in both arms, but minimal movement in both legs. Blood tests revealed higher-than-normal levels of carbon dioxide and an acidification of the blood. A CT scan of the chest showed signs consistent with aspiration, but no evidence of pulmonary embolism, or a blood clot in the lungs. Nevertheless, she received invasive breathing support.
Apart from high blood pressure in the past, her medical history was unremarkable, with no family history of genetic conditions, breathing problems, or muscle weakness.
Electromyography, which detects alterations in muscles’ electrical activity, suggested an inflammatory muscle disease. As such, she was treated with the immunosuppressant methylprednisolone and inflammation-reducing immunoglobulin (antibodies), but showed minimal improvement.
Biochemical and molecular genetic testing is crucial for diagnosing late-onset Pompe disease, as starting enzyme replacement therapy early is key to improving outcomes and quality of life.
A biopsy of the biceps muscle in the arm subsequently ruled out an inflammatory disease and showed abnormalities in muscle fibers. As a result, methylprednisolone therapy was stopped. A week later, she developed respiratory failure and was re-intubated and underwent a tracheostomy, a surgical procedure to create a small hole in the windpipe.
After sending biopsied muscle tissue to a specialist for analysis, the report described a chronic muscle disease marked by excess glycogen. Further blood tests revealed very low levels of acid alpha-glucosidase enzyme activity alongside two mutations in the GAA gene.
These findings confirmed an LOPD diagnosis, prompting a plan for enzyme replacement therapy with Nexviazyme (avalglucosidase alfa), which provides the body with a source of the enzyme, in an outpatient setting.
“Biochemical and molecular genetic testing is crucial for diagnosing late-onset Pompe disease, as initiating enzyme replacement therapy early is key to improving outcomes and quality of life,” the team recommended.
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