Pompe disease is caused by a deficiency in acid alpha-glucosidase (GAA), which causes the accumulation of glycogen in the muscles, leading to progressive, irreversible muscle damage. 

The disease is typically classified into 2 categories: infantile and late-onset forms. In this article, we will be looking at how enzyme replacement therapy affects outcomes in late-onset Pompe disease (LOPD). 

Attenuating Clinical Progression of LOPD 

Toscano and Schoser conducted a systematic literature review on the role of enzyme replacement therapy in managing LOPD. They included studies that involved patients with Pompe disease aged 2 or more years and excluded nonhuman studies.


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They reported that most LOPD patients received alglucosidase alfa at a dose of 20 mg/kg every other week. Creatine kinase levels were elevated in patients with LOPD and were an excellent indicator for diagnosis and treatment response. The 6-minute walking test was universally accepted as a key outcome measure for motor function. 

Toscano and Schoser wrote, “In untreated LOPD patients, the probability of wheelchair use increases—on average — by 13% each year after diagnosis.” This extraordinarily high figure highlights the severe morbidity risk that LOPD patients face if they are diagnosed or started on treatment too late. 

Read more about Pompe disease epidemiology 

Most patients who were on enzyme replacement therapy still had impaired ambulation, with 70.4% needing walking assistance. Intriguingly, the research team found 7 patients in the medical literature reported experiencing improvements in ambulation following the commencement of therapy. However, given that Pompe disease is progressive in nature, a plateauing of symptoms would be enough to be considered a treatment success. 

The researchers also found that the likelihood of needing ventilation support increases by an average of 8% per year for untreated LOPD patients. On the other hand, 59.1% of patients on enzyme replacement therapy experienced improvements in their respiratory status, with 36.4% achieving stabilization. 

In their study, published in the Journal of Neurology, Toscano and Schoser concluded, “The findings of our analysis indicate that alglucosidase alfa treatment offers an effective, safe, and well tolerated therapy that attenuates clinical progression in most patients with LOPD.”

A number of studies demonstrate that the impact of enzyme replacement therapy on Pompe disease patients has been overwhelmingly positive, resulting in improved quality of life and better survival. The literature review conducted by Toscano and Schoser contrasted the benefits of alglucosidase treatment with the downsides of not being on treatment. Studies have time and again demonstrated that the cost of not being on enzyme replacement therapy is immense. 

The impact of enzyme replacement therapy has been so notable that Chan and colleagues wrote that “the natural history of LOPD is now developing as a treatable disease.” Ironically, the increased longevity of LOPD patients has allowed symptoms other than progressive muscle weakness to develop. They wrote, “With the advent of [enzyme replacement therapy] and the concurrent increase in the scientific study of LOPD, the condition once primarily conceptualized as a limb-girdle muscle disease with prominent respiratory involvement is increasingly recognized to be a condition that results in signs and symptoms across body systems and structures.” 

How Newborn Screening Can Make a Difference 

Given these findings, it would be reasonable to think that the implementation of newborn screening for Pompe disease would result in better clinical outcomes for patients. Lee and colleagues conducted a prospective observational cohort study to investigate the outcomes of LOPD patients who have been identified through newborn screening and have been treated with enzyme replacement therapy. 

The research team studied data from newborn screening for Pompe disease that has been implemented in Taiwan since 2005. LOPD was defined as all cases that had low GAA activity but no cardiac involvement at the time of diagnosis. Patients who developed signs and symptoms of Pompe disease, such as elevated creatine kinase, cardiac involvement, or developmental delay, were treated with enzyme replacement therapy and followed-up every few months. Various developmental assessments were carried out, including the 6-minute walking test and other motor function tests. 

The results of the study demonstrated that all patients experienced improvements in their physical performance and endurance after receiving treatment. For patients that did not receive treatment, nonprogressive hypotonia, muscle weakness, and impairment in physical fitness tests have been reported. 

Read more about Pompe disease treatment 

Lee and colleagues wrote, “Our data support that patients with LOPD identified through [newborn screening] who were genotypically similar to the clinical cases improved biochemically and clinically after early ERT.” Nevertheless, treated patients still generally performed poorly in the sit-up test, owing to abdominal and pelvic muscle weakness. 

Putting all the above research together, we can conclude the following: LOPD patients experience better outcomes when prescribed enzyme replacement therapy, and one of the best means to ensure that LOPD patients receive enzyme replacement therapy early is to conduct newborn screening of Pompe disease. 

It is important to note that starting enzyme replacement therapy does not completely eliminate all the signs and symptoms of Pompe disease, as residual muscle weakness remains. In addition, more systems may become involved as the disease progresses. However, at present, enzyme replacement therapy represents the best strategy for managing Pompe disease and preventing further deterioration. 

Hence, a strong public health step would be to advocate for Pompe disease newborn screening for every infant across the world. Scientists are confident that this will detect many more cases of Pompe disease and allow physicians to initiate treatment early, saving lives in the process. 

References

Toscano A, Schoser B. Enzyme replacement therapy in late-onset Pompe disease: a systematic literature reviewJ Neurol. 2013;260(4):951-959. doi:10.1007/s00415-012-6636-x

Chan J, Desai AK, Kazi ZB, et al. The emerging phenotype of late-onset Pompe disease: a systematic literature reviewMol Genet Metab. 2017;120(3):163-172. doi:10.1016/j.ymgme.2016.12.004

Lee NC, Chang KL, In ‘t Groen SLM, et al. Outcome of later-onset Pompe disease identified through newborn screeningJ Pediatr. 2022;S0022-3476(21)01279-8. doi:10.1016/j.jpeds.2021.12.072