Case study describes woman’s late-onset Pompe diagnosis
Atypical, slowly progressive disease posed 'diagnostic challenge,' researchers say
A woman in Canada with atypical and slowly progressive onset of muscle weakness affecting her eyelids, face, and throat muscles had shown symptoms for decades before being diagnosed with late-onset Pompe disease (LOPD), according to a study describing her case.
Doctors considered several neuromuscular diseases before arriving at the Pompe disease diagnosis based on broad genetic testing and a dried blood spot. This test detects the activity of the GAA enzyme, the protein that’s missing or faulty in people with Pompe disease.
“Clinicians should have a low threshold to screen patients with dried blood spot testing before muscle biopsies, as blood spot testing is more sensitive for diagnosing Pompe disease,” the researchers wrote. “The availability of enzyme replacement therapy with potential disease-altering impact has heightened the impetus for timely diagnosis of Pompe disease,” they added.
The case was described in the study, “Late-onset Pompe disease mimicking oculopharyngeal muscular dystrophy,” published in Practical Neurology.
Pompe disease is caused by mutations in the GAA gene that lead to missing or dysfunctional acid alpha-glucosidase (GAA), an enzyme needed to break down glycogen, a complex sugar molecule. This results in the abnormal accumulation of glycogen inside cells, particularly in muscle cells, impairing their function.
LOPD symptoms include weakness, breathing difficulties
In LOPD, symptoms appear after the first year of life and typically include progressive muscle weakness and breathing problems.
The researchers described the case of a woman in her late 70s with atypical, slowly progressive symptoms that started in her 40s. Her Pompe symptoms included difficulty swallowing solids and liquids, difficulty speaking with tongue and facial weakness, and droopy eyelids, or ptosis, affecting both eyes and her visual field.
The woman had undergone eyelid-lift surgery four years earlier. More recently, she had developed muscle weakness without pain, mainly affecting her core muscles. This led to issues with bending forward and sitting up.
On examination, the researchers found the woman had audible, thick lung secretions and drooling, as well as facial and tongue weakness affecting speech. She also had mild weakness in the upper and lower limbs and mild gait issues.
Initial testing excluded autoimmune or inflammatory conditions, including myasthenia gravis, which a maternal cousin had. Electromyography testing used to detect alterations in muscles’ electrical activity suggested myopathy, a term used for any condition affecting the muscles that control voluntary movements.
Considering the time course, the woman’s ptosis (eyelid drooping) and the lack of damage in specialized nerve cells called motor neurons, an amyotrophic lateral sclerosis diagnosis was unlikely, said the researchers. Genetic testing also excluded oculopharyngeal muscular dystrophy (OPMD) and myotonic dystrophy.
Broader genetic testing for neuromuscular diseases identified two disease-causing mutations in the GAA gene, one in each gene copy. A dried blood spot test confirmed decreased GAA activity, leading to a diagnosis of LOPD.
“Pompe disease is relatively easily identified using dried blood spot testing as a screening test,” the researchers wrote. In the appropriate clinical context, “clinicians should consider dried blood spot testing early in the workup for undifferentiated myopathies,” they said.
The woman died of an unrelated cause while applying to receive enzyme replacement therapy, a treatment approach that provides an engineered form of the GAA enzyme.
“This patient’s presentation posed a diagnostic challenge, and we considered several genetic/metabolic myopathies,” the team wrote. “In particular, her condition quite closely mimicked a typical OPMD presentation.”
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