Purpose of review

This review summarizes the clinical presentation and provides an update on the current strategies for diagnosis of Pompe disease. We will review the available treatment options. We examine newly approved treatments as well as upcoming therapies in this condition. We also provide commentary on the unmet needs in clinical management and research for this disease.

Recent findings

In March 2015, Pompe disease was added to the Recommended Uniform Screening Panel (RUSP) and since then a number of states have added Pompe disease to their slate of diseases for their Newborn Screening (NBS) program. Data emerging from these programs is revising our knowledge of incidence of Pompe disease. In 2021, two randomized controlled trials involving new forms of enzyme replacement therapy (ERT) were completed and one new product is already FDA-approved and on the market, whereas the other product will come up for FDA review in the fall. Neither of the new ERT were shown to be superior to the standard of care product, alglucosidase. The long-term effectiveness of these newer forms of ERT is unclear. Newer versions of the ERT are in development in addition to multiple different strategies of gene therapy to deliver GAA, the gene responsible for producing acid alpha-glucosidase, the defective protein in Pompe Disease. Glycogen substrate reduction is also in development in Pompe disease and other glycogen storage disorders.

Summary

There are significant unmet needs as it relates to clinical care and therapeutics in Pompe disease as well as in research. The currently available treatments lose effectiveness over the long run and do not have penetration into neuronal tissues and inconsistent penetration in certain muscles. More definitive gene therapy and enzyme replacement strategies are currently in development and testing.

Objective: Left atrial (LA) dilatation and heart failure are independent risk factors for ischemic stroke. The goal of this study is to evaluate the association between LA dilatation and reduced left ventricular ejection fraction (EF) with cardioembolic stroke. Methods: Four hundred fifty-three patients with ischemic stroke admitted to the University of California, Irvine between 2016 and 2017 were included based on the following criteria: age >18 and availability of echocardiogram. Stroke was categorized into cardioembolic and non-cardioembolic. EF was categorized into normal: 52-72% (male), 54-74% (female), mildly abnormal: 41-51% (male), 41-53% (female), moderately abnormal: 30-40%, and severely abnormal: <30%. LA volume was categorized into normal (≤34 ml/m²) vs. enlarged (≥35 ml/m²). Other variables included gender, hypertension [systolic blood pressure (SBP) ≥ 140 or diastolic blood pressure (DBP) ≥ 90], and known history of atrial fibrillation (Afib). Results: Two hundred eighteen patients had cardioembolic, and 235 had non-cardioembolic stroke. Among patients with cardioembolic stroke, 49 (22.4%) and 142 (65%) had reduced EF and enlarged LA, respectively, as compared with 19 (8.1%) and 65 (27.7%) patients with non-cardioembolic stroke (p < 0.0001). The odds of cardioembolic stroke were 2.0 (95% CI: 0.1-6.0) and 8.8 times (95% CI: 1.9-42.3) higher in patients with moderately and severely reduced EF, respectively, than in patients with normal EF. The odds of cardioembolic stroke was 2.4 times (95% CI: 1.5-3.9) higher in patients with enlarged LA than in patients with normal LA size. Compared with patients with normal LA and EF, patients with combined enlarged LA and reduced EF had significantly higher rates of Afib (43.4 vs. 9.0%, p < 0.0001) and cardioembolic stroke (78.3 vs. 43.4%, p < 0.0001). Conclusions: LA dilatation along with reduced EF is a reliable predictor of Afib and cardioembolic stroke. Further studies are warranted to determine the benefit of anticoagulation for secondary stroke prevention in such patient population.