Pompe Genetic Prevalence Higher in Korea Than Japan

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by Steve Bryson PhD |

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Based on a literature and database analysis, the predicted genetic prevalence of disease-related variants in the GAA gene — the underlying cause of Pompe disease — is higher in the Korean population than in Japanese, a study indicates.

The study, “Two Approaches for a Genetic Analysis of Pompe Disease: A Literature Review of Patients with Pompe Disease and Analysis Based on Genomic Data from the General Population,” was published in the journal Children.

More than 500 different mutations (variants) in the GAA gene have been found in people with Pompe disease, resulting in an absence or reduction of the acid alpha-glucosidase (GAA) enzyme. A lack of this enzyme leads to the toxic buildup of the complex sugar molecule glycogen, mainly affecting heart and muscle tissue.

Symptoms of Pompe disease can appear from birth to late adulthood, depending on the specific variant. Variants that lead to a greater loss of enzyme activity are associated with more severe disease.

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Investigating the occurrence of these variants in large populations can help predict the likelihood of developing Pompe disease.

Now, a researcher at the Kyung Hee University School of Medicine in South Korea compared GAA variants in Korean and Japanese Pompe patients reported in previous studies, to those found in unaffected carriers in the general population based on genomic databases. The incidence and prevalence of Pompe disease in the Korean population had not been investigated previously.

A literature search for Korean and Japanese patients with Pompe was conducted, and confirmed disease-related GAA variants — pathogenic or likely pathogenic variants (PLPVs) — were included in the analysis.

Information on GAA variants in unaffected carriers was collected from the Korean Reference Genome Database (KRGDB), the Japanese Multi Omics Reference Panel (jMorp), and the Genome Aggregation Database (gnomAD), which is a global database of Pompe variants.

The carrier frequency and predicted genetic prevalence were calculated based on PLPVs that were heterozygous — that is, occurring in one of the two genes inherited from each parent.

From 10 studies, 17 different GAA PLPVs were reported in 32 Korean Pompe patients. Of those, four PLPVs (23.5%) also were found in unaffected Korean carriers in the KRGDB.

A total of 29 different PLPVs were reported in 76 Japanese patients from 17 studies, and six of these PLPVs were seen in unaffected Japanese carriers in the jMorp. Only one PLPV was found in all patients and unaffected carriers.

In contrast, PLPVs found in Pompe patients occurred in 57.1% of unaffected Koreans and 46.2% of unaffected Japanese.

Certain PLPVs detected in Korean or Japanese Pompe patients were not found in any population database, which means “there are GAA variants that are enriched especially in patients, which contribute to the development of Pompe disease,” the researcher wrote.

PLPVs specific to Pompe included: c.796C>T, c.2171C>A, c.1696T>C, and c.1585_1586delinsGT (TC to GT transition). Of note, “C” denotes cytosine, “A” stands for adenine, “T” for thymine, and “G” is guanine. All are building blocks of DNA.

The overall distribution of disease severity associated with GAA PLPVs in patients was different from unaffected carriers, with more PLPVs associated with infantile Pompe disease seen in patients.

Finally, the total calculated carrier frequency for Pompe in Koreans was found to be 1.7%. The predicted genetic prevalence based on the KRGDB was one in 13,656, which refers to 7.32 cases per 100,000 births; that “is comparable to the incidence of 1:16,919 from [a newborn screening] program involving 473,738 newborn samples in Taiwan,” the researcher wrote.

In comparison, the carrier frequency for Pompe in Japanese people was found to be 0.7%, with a predicted genetic prevalence of one in 78,013, or 1.28 per 100,000 births based on jMorp.

“The relationship between GAA variants found in patients with Pompe disease and in the general population is predicted to be more than a moderate correlation,” the author concluded.