How does one define a “rare disease”? A cynic might answer, “Any disease that does not affect me or my family.” However, this thinking is short-sighted and fails to appreciate 2 things: one, a disease can still be considered rare if one is affected; two, the rarity of a disease depends heavily on a particular population—a disease considered rare in one part of the world may be considered common elsewhere. 

When I was working in Borneo, there had been a sudden outbreak of rabies in the community. It is a frightening prospect: mad dogs chasing you down until they give you the fatal bite. Most individuals choose to downplay their symptoms and only seek help when their condition has worsened considerably. The disease was making front-page news in every local paper. However, the disease was curiously contained within the perimeters of the state; in other words, it was a local, not a national, crisis. 

The key point here is that the prevalence and spread of a disease can differ greatly between locations, even if the locations belong to the same country.

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Genetic Mutation Patterns in France 

In the Journal of Inherited Metabolic Diseases, Semplicini and colleagues carried out a nationwide study that covered more than 40 years to investigate the epidemiology and characterize the GAA mutations in late-onset Pompe disease (LOPD). They obtained data from 2 main laboratories involved in the diagnosis of Pompe disease, managing to include 246 patients, with a mean age of 43 years. 

Read more about Pompe disease epidemiology 

The researchers estimated that the frequency of LOPD in France is about 1 in 69,927 newborns. Other findings included:  

  • A total of 83 different mutations were identified in the GAA gene; a total of 28 were novel. 
  • The common c.-32-13T>G mutation was found in 151/170 index cases. 
  • Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg).
  • Patients who have the c.-32-13T>G mutation had an older mean age at onset, compared to other patients. 

This epidemiological study of Pompe disease was heavily focused on the prevalence of specific genetic mutations within a population (France). These kinds of studies hold great value in the research lab, where scientists need to match up genetic mutations and diseases. 

Pediatric Involvement in India 

As published in Neuromuscular Disorders, Puri and colleagues conducted an epidemiological study on the prevalence and incidence of LOPD, this time in India. Unlike Semplicini and colleagues, their focus was on the most common presentation and progression of the disease.

They performed a retrospective study at 7 major medical centers in India between 2008 and 2020, recruiting 20 patients from 20 families. “We set out to evaluate the spectrum of phenotypic manifestations, the multisystemic nature of the disease and course of illness,” they wrote.  

Read more about Pompe disease patient education 

The Indian research team encountered a few problems worth mentioning. First, most clinical studies in the medical literature on LOPD were conducted in the Caucasian population. Second, there is no national registry or database for Pompe disease in India. Some studies have suggested that Pompe disease occurs at a very low rate among Indians, but Puri et al believed this was due to poor data collection. Hence, the research team was only able to conduct their study by requesting medical data directly from the 7 medical centers. 

Here are some of their findings: 

  • The mean age of symptom onset was around 11 years of age. 
  • The most common initial manifestation of Pompe disease was pelvic muscle girdle weakness. 
  • Proximal lower limb muscle weakness was present in all 20 patients studied. 
  • Seven of the 20 patients needed respiratory support at some point in their disease course. 
  • Eight of the 20 patients had evidence of cardiac involvement. 
  • Exon 13 and 14 were the most common exons with mutations. 
  • Twelve of the 20 patients were alive at follow-up 5 years after diagnosis. 

The study shines a light on how Pompe disease affects pediatric patients of Indian origin. Based on the report, it seems the disease course in India has much in common with descriptions from other parts of the world.

Improving Epidemiological Research

The value of putting 2 very different epidemiological studies side by side is to highlight both their similarities and their differences. For example, both studies reveal that LOPD is a rare disease that can cause severe myopathy. However, one key difference between the studies is the tools at the epidemiologists’ disposal in carrying out their research.

“In developing nations like India, testing for rare phenotypes including Pompe disease is lacking due to inadequate awareness, coupled with the limited availability of enzyme replacement therapy,” the Indian authors wrote. ”The latter limits the interest for the busy neurologist, pulmonologist or physician.”

Epidemiological studies will greatly improve if we move forward on a few important fronts. First, we need a clear, globally-accepted definition of what constitutes a “rare disease,” and that definition should be used throughout the medical literature. Second, we need to standardize how we collect epidemiological data to ensure that scientists are truly able to make apple-to-apple comparisons. Lastly, we desperately need to upgrade data-collecting capabilities in all parts of the world. With these in place, we could soon have at our fingertips a coherent, transparent, and data-rich collection of medical facts; a metaverse for scientific research, if you will.  


Semplicini C, Letard P, De Antonio M, et al. Late-onset Pompe disease in France: molecular features and epidemiology from a nationwide studyJ Inherit Metab Dis. 2018;41(6):937-946. doi:10.1007/s10545-018-0243-7

Puri RD, Setia N, N V, et al. Late onset Pompe Disease in India – beyond the Caucasian phenotypeNeuromuscul Disord. 2021;31(5):431-441. doi:10.1016/j.nmd.2021.02.013