Late-onset Pompe disease (LOPD) can have a heterogeneous clinical presentation that can complicate diagnosis, especially when less common initial symptoms are present before musculoskeletal weakness, according to a review article published in the Polish Journal of Neurology and Neurosurgery.

The current recommendation is to screen patients for LOPD if they have a moderate increase in creatine kinase (CK) levels, limb-girdle weakness, rigid-spine syndrome, or weakness of the diaphragm muscles unless there is a clear differential diagnosis. Initial screening usually involves the evaluation of acid alpha-glucosidase (GAA) activity followed by genetic screening of the GAA gene.

“Patients who manifest with musculoskeletal and respiratory symptoms are prone to be diagnosed sooner than individuals with nonmuscular symptoms, and therefore it is important to raise awareness of other manifestations of this disease,” the authors said.

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In addition to the more common neuromuscular, skeletal, and respiratory symptoms previously mentioned, patients may also experience cardiovascular, gastrointestinal, urinary tract, and vascular system involvement.

Read more about the differential diagnosis of Pompe disease.

Cardiovascular symptoms can include supraventricular arrhythmias such as Wolff Parkinson White syndrome (WPW syndrome), supraventricular tachycardia (SVT), sick sinus syndrome, and atrial fibrillation. Rarely, LOPD patients may experience hypertrophic cardiomyopathy.

Incontinence, diarrhea, abdominal pain, cramps, stool urgency, early satiety, macroglossia, dysphagia, and dysarthria can all be gastrointestinal symptoms of LOPD. The smooth muscles of the genitourinary tract may also be involved in LOPD and lead to urinary urge incontinence and other lower urinary tract symptoms.

Accumulation of glycogen in blood vessels can also lead to a number of vascular symptoms including dilative arteriopathy, aneurysms, ischemic stroke, lacunar encephalopathy, subarachnoid hemorrhage, and aortic stiffness.

“A high index of suspicion among neurologists consulting internal medicine wards would aid early diagnosis of LOPD, while a multidisciplinary approach with the involvement of other specialists can reduce the risk of complications and improve the prognosis for LOPD patients,” the authors suggested.


Jastrzębska A, Kostera-Pruszczyk A. Multisystem presentation of late onset Pompe disease: what every consulting neurologist should know. Neurol Neurochir Pol. Published online December 7, 2022. doi:10.5603/PJNNS.a2022.0075