The range of genes linked to glycogen storage diseases (GSDs), including Pompe disease and Cori disease, among others, expands, a new study suggests.

There were 18 gene variants identified in Chinese patients with GSD using whole exome sequencing. The gene variants were in the GAA, AGL, PHKA2, and PYGL genes, and 9 of them were novel, reported Rui Dong, of the Shandong University in Jinan, China, and colleagues.

“Our study expanded the variation spectrum of gene[s] associated with GSDs,” the study authors wrote. “Next-generation sequencing was considered the preferred diagnostic method for GSD because invasive liver biopsy can be avoided.”

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The results were published in the journal Frontiers in Genetics.

Read more about the etiology of Pompe disease

GSD is the name given to a group of diseases characterized by the accumulation of glycogen in the liver and muscles. It is caused by a mutation in a gene coding for one of the enzymes that is necessary to break down glycogen and form glucose. Pompe disease, caused by a mutation in the GAA gene, is one of the most common forms of GSD, mostly affecting East-Asian populations. 

The study team assessed 12 patients with suspected glycogen storage disease. The patients’ parents were also enrolled in the study.

The patients’ laboratory and clinical data were examined. Whole exome sequencing was used to find causal gene variations in the patients, and Sanger sequencing was used to confirm the findings.

Following genetic testing, 7 of them were diagnosed with Pompe disease (GSD type II) while 2 were diagnosed with GSD type III (Cori disease), 1 diagnosed with GSD type IV, and 2 diagnosed with GSD type IXα.  

Of the 18 variants, 11 were in the GAA gene, 3 were in the AGL gene, 2 were in the PYGL gene, and 2 were in the PHKA2 gene.

Using bioinformatics tools, the researchers predicted that 8 of the novel variants were disease-causing. They also predicted that 4 of the variants in the GAA gene could affect the function of the protein by destroying hydrogen bonds or leading to conformational constraints.

The researchers concluded that whole exome sequencing, together with clinical, biochemical, and pathological data, “could provide accurate results for diagnosing and sub-typing GSD and related diseases in [the] clinical setting.”


Dong R, Wei X, Zhang K, et al. Genotypic and phenotypic characteristics of 12 Chinese children with glycogen storage diseases. Front Genet. 2022;29;13:932760. doi:10.3389/fgene.2022.932760