Pompe disease is caused by an acid alpha-glucosidase (GAA) deficiency. The estimated incidence of Pompe disease varies by ethnicity and geographical region. 

Pompe Disease in Asia

The highest genetic prevalence for GAA deficiency is observed in the East Asian population at 1 in 12,125.1 In Taiwan, the incidence rate is lower and is estimated to be 1 in 34,348.2 

Pompe Disease in Europe

Finland has a population of approximately 5 million and has the lowest incidence of GAA deficiency, with only 2 reported cases of infantile Pompe disease and 1 case of adult-onset.3 The incidence in the Netherlands was estimated to be 1 in 40,000. Newborns were screened using newborn Guthrie cards and analyzed for the 3 most common mutations (IVS1(-13T→G), 525delT, and delexon18) seen in GAA deficiency in the Dutch population. Other mutations that account for milder disease and presentation in adulthood were not considered, so the true incidence is likely higher.4 

Pompe Disease in North America

In the United States, one study found the incidence of GAA deficiency disease to be higher than previously published estimates. Results from 219,973 newborns in Illinois revealed a prevalence rate of 1 in 21,979.5 Another study of 108,905 newborns in Washington reported a prevalence of 1 in 27,800.6 

In Mexico, one study detected 11 cases of GAA deficiency disease in a sample of 20,018 patients for an incidence rate of 1 in 20,018 over the course of 3 years.7 

Carrier Frequency and Predictive Genetic Prevalence by Population

One study estimated the carrier frequency (CF) and predictive genetic prevalence (pGP) of GAA deficiency by region. The authors analyzed variants of the GAA gene using the GnomAD (v2.1.1) database in unrelated Africans/African Americans (12,487), Latino/admixed Americans (17,720), Ashkenazi Jews (5185), East Asians (9977), Finnish (12,562), non-Finnish Europeans (64,603), South Asians (15,308), and others (3614). A total of 3270 genetic variations of GAA were identified, of which 154 were classified as pathogenic or likely pathogenic variants (PLPVs) (Table 1).1 

Table 1. Most frequently identified pathogenic or likely pathogenic variants and corresponding allele frequency in different populations

PopulationMost Frequently Identified PLPVs to GAA (allele frequency)Group
African/African Americanc.2560C >T (0.00189)A, B, C
Latino/admixed Americanc.-32-13T>G (0.00269)B, C
Ashkenazi Jewishc.-32-13T>G (0.00554)B, C
East Asian[c.752C >T; c.761C >T] (0.00276)B
Finnishc.1725C >A (0.00020)Unknown
Non-Finnish European*c.-32-13 T >G (0.00529)B, C
South Asiac.-32-13 T >G (0.00190)B, C
Globalc.-32-13 T >G (0.00340)B, C

*c.-32-13 T >G (0.00529), c.2238G >C (0.00057), and c.841C >T (0.00041) shared similar prevalence rates. 

†Group A: symptom onset ≤ 12 months of age with cardiomyopathy (patients classified as classic infantile Pompe disease); Group B: symptom onset at ≤ 12 years of age without cardiomyopathy; Group C: onset >12 years of age.8

Overall results were as follows1:

  • Unaffected carriers for GAA (the total CF for GAA) in the overall population is predicted to be 1.3%. 
  • Of the 7 population groups, East Asians showed the highest CF (1.8%), followed by non-Finnish Europeans (1.7%), Ashkenazi Jews (1.3%), Africans/African Americans (1.2%), Latinos/admixed Americans (0.8%), South Asians (0.7%), and Finnish (0.2%). 
  • Overall, the pGP for GAA deficiency was 1 in 23,232. 
  • The pGP of East Asians was 1 in 12,125 births, followed by non-Finnish Europeans (1 per 13,756 births), Ashkenazi Jews (1 per 22,851 births), Africans/African Americans (1 per 26,560 births), Latino/admixed Americans (1 per 57,620 births), South Asians  (1 per 93,087 births), and Finnish (1 per 1,056,444 births).

References

 1. Park KS. Carrier frequency and predicted genetic prevalence of Pompe disease based on a general population database. Mol Genet Metab Rep. 2021;27:100734. doi:10.1016/j.ymgmr.2021.100734

2. Chien YH, Lee NC, Thurberg BL, et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009;124(6):e1116-e1125. doi:10.1542/peds.2008-3667

3. Palmio J, Auranen M, Kiuru-Enari S, Löfberg M, Bodamer O, Udd B. Screening for late-onset Pompe disease in Finland. Neuromuscul Disord. 2014;24(11):982-985. doi:10.1016/j.nmd.2014.06.438

4. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease type II in the Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. 1999;7(6):713-716. doi:10.1038/sj.ejhg.5200367

5. Burton BK, Charrow J, Hoganson GE, et al. Newborn screening for lysosomal storage disorders in Illinois: the initial 15-month experience. J Pediatr. 2017;190:130-135. doi:10.1016/j.jpeds.2017.06.048

6. Scott CR, Elliott S, Buroker N, et al. Identification of infants at risk for developing Fabry, Pompe, or mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry. J Pediatr. 2013;163(2):498-503. doi:10.1016/j.jpeds.2013.01.031

7. Navarrete-Martínez JI, Limón-Rojas AE, Gaytán-García MDJ, et al. Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: three-year findings from a screening program in a closed Mexican health system. Mol Genet Metab. 2017;121(1):16-21. doi:10.1016/j.ymgme.2017.03.001

8. Reuser AJJ, van der Ploeg AT, Chien YH, et al.; On Behalf Of The Pompe Registry Sites. GAA variants and phenotypes among 1,079 patients with Pompe disease: data from the Pompe registry. Hum Mutat. 2019;40(11):2146-2164. doi:10.1002/humu.23878

Reviewed by Debjyoti Talukdar, MD, on 7/27/2021.

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