Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Pompe disease (PD) is a rare inherited recessive autosomal disorder caused by pathogenic nucleotide variants within the gene GAA , encoding Acid alpha-glucosidase (GAA), the lysosomal enzyme catalyzing glycogen breakdown to glucose. Methods We performed molecular screening in a cohort of 15,068 participants with suspected PD of a wide range of age from several regions of Russia. Two screenings had been undertaken from 2014 to 2025, and 2021 to 2025, respectively: 13,128 patients were screened using “two-tier one-gene” algorithm (measurement of GAA activity in dried blood spots followed by Sanger sequencing of the GAA) and 1940 patients were screened using Next-Generation Sequencing (NGS)-based algorithm (NGS of the panel of genes linked to neuromuscular disorders, ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCD, SGCG, TCAP , and GAA , followed by measurement of GAA activity when needed). Results 63 causative nucleotide variants in the GAA gene were detected, the most common being c.-32-13T>G (28 patients) followed by c.2662G>T (10 patients). 25 novel nucleotide variants in the GAA gene were described. Of 1,940 patients screened using an NGS-based algorithm, 138 patients (7.1%) were diagnosed with various muscular dystrophies, myopathies, or PD. The majority of these individuals had biallelic variants in the CAPN3 gene (30%), indicative of calpainopathy. Total 57 (0.47%) and 8 (0.41%) patients were diagnosed with PD as a result of “two-tier one-gene” or NGS-based algorithms, respectively. Discussion Overall, our study is the first large-scale country-wide selective screening for PD in Russia based on sequencing and GAA activity measurement and providing the most comprehensive overview of genetics of PD in this study population.
Authors: Aleksander Pushkov, Daria Chudakova, Ilya Zhanin, Sergey Nikitin, Elena Basargina, Lydmila Kuzenkova, Daria Andreeva, Maria Vasil’eva, Sergey Vasichkin, Albina Gabitova, Elena Gaisina, Elena Saifullina, Amina Gamzatova, Olga Gilvanova, Vyacheslav Dudin, Olga Ergina, Sergey Kurbatov, Elena Noskova, Elena Osipova, Olga Tihonova, Ekaterina Fedotova, Evgeny Nuzhny, Viktoria Chernikova, Anastasia Yamshchikova, Lubov Kyzina, Natalia Irinina, Olga Rohlenko, Yulia Kutkova, Natalia Popkova, Alsy Ahunova, Alina Alexeeva, Natalia Mazanova, Nataliya Sdvigova, Leyla Gandaeva, Olga Zharova, Tatyana Podkletnova, Alexey Sukhozhenko, Anastasia Rusakova, Dmitry Demianov, Aleksandr Pakhomov, Andrey Fisenko, Kirill Savostyanov
Institutions: Ministry of Health of the Russian Federation, Scientific Center of Children's Health, Research Centre for Medical Genetics, Children's City Clinical Hospital №11, Central Clinical Hospital and Polyclinic, Moscow Clinical Scientific Center, Voronezh State Medical Academy named after N.N. Burdenko, Immanuel Kant Baltic Federal University, Research Center of Neurology, Samara State Medical University, Ulyanovsk Regional Clinical Hospital, Russian Academy of Sciences, Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7126061528