Pompe disease rates vary by region; ethnicity seen playing role
Rates higher in areas with large populations of people of African descent
Estimates of the number people diagnosed with Pompe disease vary widely across regions, with notably higher rates in populations of African descent, a study review found.
The researchers attributed the variability to underlying genetic differences as well as inconsistencies in diagnostic criteria, newborn screening methods, and disease classification depending on geographic region, factors that make it difficult to estimate Pompe disease rates worldwide.
This “highlights the need to standardize screening and diagnosis methods, genetic testing protocols, and uniform disease classification,” the researchers wrote.
The study, “Global variations in diagnostic methods and epidemiological estimates in Pompe disease: findings from a scoping review,” was published in the Orphanet Journal of Rare Diseases.
Pompe disease is caused by mutations in the GAA gene, which results in a deficiency of the enzyme acid alpha-glucosidase (GAA). Without enough working GAA enzyme, a sugar molecule called glycogen builds up in various tissues, causing Pompe symptoms that can appear in infancy (infantile-onset Pompe disease, or IOPD), or in people aged 1 or older (late-onset Pompe disease, or LOPD).
Tracking disease rates to ensure prompt treatment
Pompe is diagnosed by measuring the activity of the GAA enzyme in the blood, generally followed by genetic testing to confirm mutations in the GAA gene. In many countries, Pompe is detected at birth through newborn screening.
Pompe disease prevalence, or the total number of people living with the disease, and incidence, or the number of new cases diagnosed during a specific time, are not clearly defined. Estimates vary significantly across countries and populations, partly due to differences in how the disease is diagnosed and classified.
“With the widespread availability of [enzyme replacement therapy], establishing reliable estimates of Pompe disease prevalence is essential for ensuring that patients are diagnosed and treated promptly,” the researchers wrote.
The team searched for studies in July 2023, and validated their literature search in June 2024. They looked at studies published within five years that clearly defined the group of people being studied, provided definitions of IOPD and LOPD based on age at symptom onset, and reported prevalence, incidence, or birth prevalence (the number of babies born with the disease among the total number of infants screened) using accepted definitions. They said they included studies with any GAA cutoff value, “as consensus for GAA cutoff values is lacking.”
Out of 1,210 scientific abstracts identified, 11 met all inclusion criteria.
In these studies, Pompe disease was mainly diagnosed by testing newborns’ GAA enzyme activity, followed by genetic testing to confirm the diagnosis. In some cases, patients were diagnosed based on clinical Pompe disease symptoms, with enzyme tests and often genetic tests used to confirm the disease. However, enzyme activity cutoff values varied widely.
Findings showed that birth prevalence varied significantly across countries. For IOPD, rates ranged from 1 in 297,387 in Japan to 1 in 62,186 in Taiwan. For LOPD, birth prevalence ranged from 1 in 82,914 in Taiwan to 1 in 17,133 in Pennsylvania.
When unconfirmed LOPD cases, such as suspected cases, were included, the numbers ranged from 1 in 42,842 in Japan to 1 in 657 in Washington, D.C.
Two studies reported Pompe disease prevalence without distinguishing between IOPD and LOPD. One found a genetically confirmed rate of 1 in 20,018 in Mexico, while the other reported mostly unconfirmed cases at a rate of 1 in 424,000 in New Zealand.
Data from the French National Pompe Registry showed a clear increase in LOPD diagnoses in France, from 2.6 per year before 2001 to 10.6 per year from 2001 to 2010, and 12.8 per year from 2011 to 2015.
Genetic background and ancestry significantly influenced diagnosis rates, the researchers found. Three studies reported higher rates among people of African descent.
In California, the prevalence among African-American newborns was 1 in 18,700, compared with an overall birth prevalence rate of 1 in 25,175. In Washington, D.C., where the population is predominantly African-American, the confirmed LOPD prevalence was 1 in 2,628.
A particularly high incidence was observed in the Maroon community of French Guiana, where 1 in 4,258 births was affected by IOPD. The researchers said this could be mostly due to a double founder effect, in which genetic mutations become more common in small, isolated populations over generations, leading to higher disease rates.
In contrast, studies involving Asian populations identified a high frequency of pseudo-deficiency alleles, genetic variants that alter the GAA protein or its production but do not cause the disease. In California, a specific was variant found in 1 in every 2,300 newborns of Asian/Pacific Islander descent.
“Higher [enzyme] cut-off values without genetic confirmation increase the chance of patients with pseudo-deficiency alleles (common in Taiwan and the United States) erroneously being diagnosed with Pompe disease and skewing estimates,” the researchers wrote.
“In summary, this scoping review showed that prevalence estimates differ for IOPD and LOPD and vary widely by geographic region, potentially by race and ethnicity,” the researchers concluded. “Most importantly, it highlights the need for uniformity in diagnostic and screening methods, disease classification, counselling, and family care. Continued efforts are needed to refine and standardize screening and diagnosis methods, genetic testing protocols, and the differentiation of IOPD from LOPD.”
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