neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2021-2-4-203-215neurojour-53Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSСелективный скрининг и молекулярная характеристика российских пациентов с болезнью ПомпеSelective screening and molecular characteristics of Russian patients with Pompe diseasehttps://orcid.org/0000-0003-4885-4171СавостьяновК. В.SavostyanovKirill V.noemail@neicon.ruhttps://orcid.org/0000-0001-6648-2063ПушковА. А.PushkovAlexander A.noemail@neicon.ruhttps://orcid.org/0000-0002-0144-2885БасаргинаЕ. Н.BasarginaElena N.noemail@neicon.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛ. М.KuzenkovaLyudmila M.noemail@neicon.ruhttps://orcid.org/0000-0002-3473-2897МазановаН. Н.MazanovaNatalia N.noemail@neicon.ruhttps://orcid.org/0000-0003-0890-7849ГандаеваЛ. А.GandaevaLeila A.noemail@neicon.ruhttps://orcid.org/0000-0003-4221-8406ЖароваО. П.ZharovaOlga P.noemail@neicon.ruhttps://orcid.org/0000-0001-5177-475XРябоваЕкатерина ЕвгеньевнаRyabovaEkaterina E.

Аспирант ФГАУ «НМИЦ здоровья детей».

e-mail: ryabchikko@gmail.com

MD, postgraduate student, National Medical Research Center of Children’s Health, Moscow, 119991, Russian Federation.

e-mail: ryabchikko@gmail.com

ryabchikko@gmail.comhttps://orcid.org/0000-0003-1423-0379ЖанинИ. С.ZhaninIlya S.noemail@neicon.ruhttps://orcid.org/0000-0001-8586-7946ФисенкоА. П.FisenkoAndrey P.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Министерства здравоохранения Российской ФедерацииNational Medical Research Center for Children’s Health20212912202124203215Copyright © Савостьянов К.В., Пушков А.А., Басаргина Е.Н., Кузенкова Л.М., Мазанова Н.Н., Гандаева Л.А., Жарова О.П., Рябова Е.Е., Жанин И.С., Фисенко А.П., 20212021Савостьянов К.В., Пушков А.А., Басаргина Е.Н., Кузенкова Л.М., Мазанова Н.Н., Гандаева Л.А., Жарова О.П., Рябова Е.Е., Жанин И.С., Фисенко А.П.Savostyanov K.V., Pushkov A.A., Basargina E.N., Kuzenkova L.M., Mazanova N.N., Gandaeva L.A., Zharova O.P., Ryabova E.E., Zhanin I.S., Fisenko A.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/53Введение

Введение. Болезнь Помпе (БП), или гликогеноз II типа — редкая мультисистемная наследственная болезнь накопления, вызываемая дефицитом фермента кислой мальтазы (кислой альфа-1,4-глюкозидазы), сниженная активность которой приводит к накоплению гликогена в различных органах и тканях организма.

Цель исследования — разработка высокопроизводительного метода ранней биохимической диагностики БП и оптимизация её молекулярно-генетической диагностики.

Материал и методы

Материал и методы. Характеристика относительных частот и спектра выявленных мутаций были изучены при использовании выборки из 7670 пациентов с подозрением на БП, поступивших в ФГАУ «НМИЦ здоровья детей» в рамках селективного скрининга, а также 8 пациентов с БП, лабораторный диагноз которым был поставлен вне рамок данного скрининга.

Результаты

Результаты. В результате селективного скрининга БП у российских пациентов из групп высокого риска выявляемость составила 0,47%. Приведены клинические и возрастные характеристики детей и взрослых с БП, а также вычислены относительные частоты и охарактеризован спектр 47 патогенных вариантов гена GAA, ответственных за возникновение и развитие БП, у 44 пациентов. Выявлены и изучены 17 новых мутаций гена GAA, не описанные ранее, что пополняет базу данных HGMD на 2,7%. 

Заключение

Заключение. Предложена оптимизация алгоритма молекулярной диагностики БП у российских пациентов.

Introduction

Introduction. Pompe disease (PD) or type II glycogenosis is a rare multisystem hereditary accumulation disease caused by a deficiency of the enzyme acid maltase (acid alpha-1,4-glucosidase), which leads to reduced activity to the accumulation of glycogen in various organs and tissues of the body.

The aim of the study is to develop a high-performance method of early biochemical diagnosis of PD and optimization of its molecular genetic diagnosis.

Materials and methods

Materials and methods. The characteristics of the relative frequencies and spectrum of the detected mutations were studied using a  sample of 7670 patients with suspected Pompe disease admitted to the National Medical Research Center of Children’s Health of the Ministry of Health of Russia as part of the selective screening, as well as eight patients with PD, whose laboratory diagnosis was made outside the framework of this selective screening.

Results

Results. As a result of selective screening of PD in Russian patients from high-risk groups, the detectability was 0.47%. PD’s clinical and age characteristics in both children and adults are described. The relative frequencies are calculated, and the spectrum of 47 pathogenic variants of the GAA gene responsible for the occurrence and development of Pompe disease in 44 patients is characterized. Seventeen new mutations of the GAA gene, unknown previously, have been identified and described, adding 2.7% to the HGMD database.

Conclusion

Conclusion. Optimization of the algorithm of molecular diagnosis of Pompe disease in Russian patients is proposed.

болезнь Помпеселективный скринингтандемная масс-спектрометриясеквенированиемутацииген GAAPompe diseaseselective screeningtandem mass spectrometrysequencingmutationsGAA geneReferencesСоюз педиатров России; Российское общество медицинских генетиков. Клинические рекомендации: Болезнь Помпе. МКБ 10: Е74.0. М.; 2017. Available at: https://www.pediatr-russia.ru/information/klin-rek/deystvuyushchie-klinicheskie-rekomendatsii/Болезнь%20Помпе%20СПР_17.04.17.pdfUnion of Pediatricians of Russia; Russian Society of Medical Geneticists. Clinical Recommendations: Pompe disease. ICD 10: E74.0 [Klinicheskie rekomendatsii: Bolezn’ Pompe. MKB 10: E74.0]. Moscow; 2017. Available at: https://www.pediatr-russia.ru/information/klin-rek/deystvuyushchie-klinicheskie-rekomendatsii/Болезнь%20Помпе%20СПР_17.04.17.pdf (in Russian)Hirschhorn R., Reuser A.J.J. Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In: Desnick R.J., Ioannou Y.A., Eng C.M., Scriver C.R., Beaudet A.L., Sly W.S., et al. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill, 2001: 3389-420.Hirschhorn R., Reuser A.J.J. Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In: Desnick R.J., Ioannou Y.A., Eng C.M., Scriver C.R., Beaudet A.L., Sly W.S., et al. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill, 2001: 3389–420.Pinto R., Caseiro C., Lemos M., Lopes L., Fontes A., Ribeiro H., et al. Prevalence of lysosomal storage diseases in Portugal. Eur. J. Hum. Genet. 2004; 12(2): 87-92. https://doi.org/10.1038/sj.ejhg.5201044Pinto R., Caseiro C., Lemos M., Lopes L., Fontes A., Ribeiro H., et al. Prevalence of lysosomal storage diseases in Portugal. Eur. J. Hum. Genet. 2004; 12(2): 87–92. https://doi.org/10.1038/sj.ejhg.5201044Martiniuk F., Chen A., Mack A., Arvanitopoulos E., Chen Y., Rom W.N., et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am. J. Med. Genet. 1998; 79(1): 69-72. https://doi.org/10.1002/SICI1096-86281998082779:1<69::AID-AJMG16>3.0.CO;2-KMartiniuk F., Chen A., Mack A., Arvanitopoulos E., Chen Y., Rom W.N., et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am. J. Med. Genet. 1998; 79(1): 69–72. https://doi.org/10.1002/SICI1096-86281998082779:1<69::AID-AJMG16>3.0.CO;2-KLin C.Y., Hwang B., Hsiao K.J., Jin Y.R. Pompe’s disease in Chinese and prenatal diagnosis by determination of α-glucosidase activity. J. Inherit. Metab. Dis. 1987; 10(1): 11-7. https://doi.org/10.1007/BF01799482Lin C.Y., Hwang B., Hsiao K.J., Jin Y.R. Pompe’s disease in Chinese and prenatal diagnosis by determination of α-glucosidase activity. J. Inherit. Metab. Dis. 1987; 10(1): 11–7. https://doi.org/10.1007/BF01799482Ausems M.G., Verbiest J., Hermans M.P., Kroos M.A., Beemer F.A., Wokke J.H., et al. Frequency of glycogen storage disease type II in the Netherlands: implications for diagnosis and genetic counseling. Eur. J. Hum. Genet. 1999; 7(6): 713-6. https://doi.org/10.1038/sj.ejhg.5200367Ausems M.G., Verbiest J., Hermans M.P., Kroos M.A., Beemer F.A., Wokke J.H., et al. Frequency of glycogen storage disease type II in the Netherlands: implications for diagnosis and genetic counseling. Eur. J. Hum. Genet. 1999; 7(6): 713–6. https://doi.org/10.1038/sj.ejhg.5200367Mechtler T.P., Stary S., Metz T.F., De Jesús V.R., Greber-Platzer S., Pollak A., et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet. 2012; 379(9813): 335-41. https://doi.org/10.1016/S0140-6736(11)61266-XMechtler T.P., Stary S., Metz T.F., De Jesús V.R., Greber-Platzer S., Pollak A., et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet. 2012; 379(9813): 335–41. https://doi.org/10.1016/S0140-6736(11)61266-XPompe J.C. Over idiopathische hypertrophie van het hart. Pompe. Ned. Tijdschr. Geneeskd. 1932; (76): 304-12.Pompe J.C. Over idiopathische hypertrophie van het hart. Pompe. Ned. Tijdschr. Geneeskd. 1932; (76): 304–12.Bischoff G. Zum klinischen bild der glykogen-speicherungs-krankheit (glykogenose). Kinderheilkd Z. 1932; (52): 722-6. https://doi.org/10.1007/BF02248461Bischoff G. Zum klinischen bild der glykogen-speicherungs-krankheit (glykogenose). Kinderheilkd Z. 1932; (52): 722–6. https://doi.org/10.1007/BF02248461Putschar M. Uber angeborene Glykogenspeicher-Krankheit des herzens. Beitr. Pathol. Anat. Allg. Pathol. 1932; (90): 222.Putschar M. Uber angeborene Glykogenspeicher-Krankheit des herzens. Beitr. Pathol. Anat. Allg. Pathol. 1932; (90): 222.Cori G.T. Enzymes and glycogen structure in glycogenosis. Osterr. Z. Kinderheilkd. Kinderfuersorge. 1954; 10(1-2): 38-42.Cori G.T. Enzymes and glycogen structure in glycogenosis. Osterr. Z. Kinderheilkd. Kinderfuersorge. 1954; 10(1–2): 38–42.Hers H.G. Alpha-glucosidase deficiency in generalize glycogen storage disease (Pompe’s disease). Biochem. J. 1963; (86): 11-6. https://doi.org/10.1042/bj0860011Hers H.G. Alpha-glucosidase deficiency in generalize glycogen storage disease (Pompe’s disease). Biochem. J. 1963; (86): 11–6. https://doi.org/10.1042/bj0860011Hoefsloot L.H., Hoogeveen-Westerveld M., Reuser A.J., Oostra B.A. Characterization of the human lysosomal alpha-glucosidase gene. Biochem. J. 1990; 272(2): 493-7. https://doi.org/10.1042/bj2720493Hoefsloot L.H., Hoogeveen-Westerveld M., Reuser A.J., Oostra B.A. Characterization of the human lysosomal alpha-glucosidase gene. Biochem. J. 1990; 272(2): 493–7. https://doi.org/10.1042/bj2720493Zhu Y., Li X., Kyazike J., Zhou Q., Thurberg B.L., Raben N., et al. Conjugation of mannose 6-phosphate-containing oligosaccharides to acid alpha-glucosidase improves the clearance of glycogen in pompe mice. J. Biol. Chem. 2004; 279(48): 50336-41. https://doi.org/10.1074/jbc.M409676200Zhu Y., Li X., Kyazike J., Zhou Q., Thurberg B.L., Raben N., et al. Conjugation of mannose 6-phosphate-containing oligosaccharides to acid alpha-glucosidase improves the clearance of glycogen in pompe mice. J. Biol. Chem. 2004; 279(48): 50336–41. https://doi.org/10.1074/jbc.M409676200Fukuda T., Ahearn M., Roberts A., Mattaliano R.J., Zaal K., Ralston E., et al. Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol. Ther. 2006; (14): 831-9. https://doi.org/10.1016/j.ymthe.2006.08.009Fukuda T., Ahearn M., Roberts A., Mattaliano R.J., Zaal K., Ralston E., et al. Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol. Ther. 2006; (14): 831–9. https://doi.org/10.1016/j.ymthe.2006.08.009Raben N., Shea L., Hill V., Plotz P. Monitoring autophagy in lysosomal storage disorders. Methods. Enzymol. 2009; (453): 417-449. https://doi.org/10.1016/S0076-6879(08)04021-4Raben N., Shea L., Hill V., Plotz P. Monitoring autophagy in lysosomal storage disorders. Methods. Enzymol. 2009; (453): 417–449. https://doi.org/10.1016/S0076-6879(08)04021-4Shea L., Raben N. Autophagy in skeletal muscle: implications for Pompe disease. Int. J. Clin. Pharmacol. Ther. 2009; 47 (Suppl. 1): 42-7. https://doi.org/10.5414/cpp47042Shea L., Raben N. Autophagy in skeletal muscle: implications for Pompe disease. Int. J. Clin. Pharmacol. Ther. 2009; 47 (Suppl. 1): 42–7. https://doi.org/10.5414/cpp47042Fuller D.D., ElMallah M.K., Smith B.K., Corti M., Lawson L.A., Falk D.J., et al. The respiratory neuromuscular system in Pompe disease. Respir. Physiol. Neurobiol. 2013; 189(2): 241-9. https://doi.org/10.1016/j.resp.2013.06.007Fuller D.D., ElMallah M.K., Smith B.K., Corti M., Lawson L.A., Falk D.J., et al. The respiratory neuromuscular system in Pompe disease. Respir. Physiol. Neurobiol. 2013; 189(2): 241–9. https://doi.org/10.1016/j.resp.2013.06.007Thurberg B.L., Lynch Maloney C., Vaccaro C., Afonso K., Tsai A.C., Bossen E., et al. Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease. Lab. Invest. 2006; 86(12): 1208-20. https://doi.org/10.1038/labinvest.3700484Thurberg B.L., Lynch Maloney C., Vaccaro C., Afonso K., Tsai A.C., Bossen E., et al. Characterization of pre- and post-treatment patho­logy after enzyme replacement therapy for Pompe disease. Lab. Invest. 2006; 86(12): 1208–20. https://doi.org/10.1038/labinvest.3700484Nascimbeni A.C., Fanin M., Masiero E., Angelini C., Sandri M. Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients. Autophagy. 2012; 8(11): 1697-700. https://doi.org/10.4161/auto.21691Nascimbeni A.C., Fanin M., Masiero E., Angelini C., Sandri M. Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients. Autophagy. 2012; 8(11): 1697–700. https://doi.org/10.4161/auto.21691Chien Y.H., Lee N.C., Huang P.H., Lee W.T., Thurberg B.L., Hwu W.L. Early pathologic changes and responses to treatment in patients with later-onset Pompe disease. Pediatr. Neurol. 2012; 46(3): 168-71. https://doi.org/10.1016/j.pediatrneurol.2011.12.010Chien Y.H., Lee N.C., Huang P.H., Lee W.T., Thurberg B.L., Hwu W.L. Early pathologic changes and responses to treatment in patients with later-onset Pompe disease. Pediatr. Neurol. 2012; 46(3): 168–71. https://doi.org/10.1016/j.pediatrneurol.2011.12.010Van der Ploeg A.T., Reuser A.J. Pompe’s disease. 2008; 372(9646): 1342-53. https://doi.org/10.1016/S0140-6736(08)61555-XVan der Ploeg A.T., Reuser A.J. Pompe’s disease. 2008; 372(9646): 1342–53. https://doi.org/10.1016/S0140-6736(08)61555-XBembi B., Cerini E., Danesino C., Donati M.A., Gasperini S., Morandi L., et al. Diagnosis of glycogenosis type II. Neurology. 2008; 71(23 Suppl. 2): S4-11. https://doi.org/10.1212/WNL.0b013e31818da91eBembi B., Cerini E., Danesino C., Donati M.A., Gasperini S., Morandi L., et al. Diagnosis of glycogenosis type II. Neurology. 2008; 71(23 Suppl. 2): S4–11. https://doi.org/10.1212/WNL.0b013e31818da91eHobson-Webb L.D., Dearmey S., Kishnani P.S. The clinical and electrodiagnostic characteristics of Pompe disease with post-enzyme replacement therapy findings. Clin. Neurophysiol. 2011; 122(11): 2312-7. https://doi.org/10.1016/j.clinph.2011.04.016Hobson-Webb L.D., Dearmey S., Kishnani P.S. The clinical and electrodiagnostic characteristics of Pompe disease with post-enzyme replacement therapy findings. Clin. Neurophysiol. 2011; 122(11): 2312–7. https://doi.org/10.1016/j.clinph.2011.04.016Zhang H., Kallwass H., Young S.P., Carr C., Dai J., Kishnani P.S., et al. Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet. Med. 2006; 8(5): 302-6. https://doi.org/10.1097/01.gim.0000217781.66786.9bZhang H., Kallwass H., Young S.P., Carr C., Dai J., Kishnani P.S., et al. Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet. Med. 2006; 8(5): 302–6. https://doi.org/10.1097/01.gim.0000217781.66786.9bСавостьянов К.В., Никитин С.С., Карпачёва К.Е. Лабораторные исследования и болезнь Помпе: От подозрения до мониторинга терапии. Нервно-мышечные болезни. 2016; 6(1): 54-62. https://doi.org/10.17650/2222-8721-2016-6-1-54-62Savost’yanov K.V., Nikitin S.S., Karpacheva K.E. Laboratory studies and Pompe disease: from suspicion to therapy monitoring. Nervno-myshechnye bolezni. 2016; 6(1): 54–62. https://doi.org/10.17650/2222-8721-2016-6-1-54-62 (in Russian)Dreyfus J., Poenaru L. White blood cells and the diagnosis of alpha-glucosidase deficiency. Pediatr. Res. 1980; (14): 342-4. https://doi.org/10.1203/00006450-198004000-00017Dreyfus J., Poenaru L. White blood cells and the diagnosis of alpha-glucosidase deficiency. Pediatr. Res. 1980; (14): 342–4. https://doi.org/10.1203/00006450-198004000-00017Wisselaar H.A., Kroos M.A., Hermans M.M., van Beeumen J., Reuser A.J. Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J. Biol. Chem. 1993; 268(3): 2223-31.Wisselaar H.A., Kroos M.A., Hermans M.M., van Beeumen J., Reuser A.J. Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J. Biol. Chem. 1993; 268(3): 2223–31.Niizawa G., Levin C., Aranda C., Blanco M., Chamoles N.A. Retrospective diagnosis of glycogen storage disease type II by use of a newborn-screening card. Clin. Chim. Acta. 2005; 359(1-2): 205-6. https://doi.org/10.1016/j.cccn.2005.04.007Niizawa G., Levin C., Aranda C., Blanco M., Chamoles N.A. Retrospective diagnosis of glycogen storage disease type II by use of a newborn-screening card. Clin. Chim. Acta. 2005; 359(1–2): 205–6. https://doi.org/10.1016/j.cccn.2005.04.007Human Gene Mutation Database (HGMD): Gene GAA. Available at: https://portal.biobase-international.com/hgmd/pro/gene.php?gene=GAAHuman Gene Mutation Database (HGMD): Gene GAA. Available at: https://portal.biobase-international.com/hgmd/pro/gene.php?gene=GAANascimbeni A.C., Fanin M., Tasca E., Angelini C. Molecular pathology and enzyme processing in various phenotypes of acid maltase deficiency. Neurology. 2008; 70(8): 617-26. https://doi.org/10.1212/01.wnl.0000299892.81127.8eNascimbeni A.C., Fanin M., Tasca E., Angelini C. Molecular pathology and enzyme processing in various phenotypes of acid maltase deficiency. Neurology. 2008; 70(8): 617–26. https://doi.org/10.1212/01.wnl.0000299892.81127.8eHuie M.L., Chen A.S., Tsujino S., Shanske S., DiMauro S., Engel A.G., et al. Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T→G) mutation in a majority of patients and a novel IVS10 (+1GT→CT) mutation. Hum. Mol. Genet. 1994; 3(12): 2231-6. https://doi.org/10.1093/hmg/3.12.2231Huie M.L., Chen A.S., Tsujino S., Shanske S., DiMauro S., Engel A.G., et al. Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T→G) mutation in a majority of patients and a novel IVS10 (+1GT→CT) mutation. Hum. Mol. Genet. 1994; 3(12): 2231–6. https://doi.org/10.1093/hmg/3.12.2231Shieh J.J., Lin C.Y. Frequent mutation of Chinese patients with infantile type of GSD II in Taiwan: evidence for a founder effect. Hum. Mutat. 1998; 11(4): 306-12. https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<306::AID-HUMU8>3.0.CO;2-SShieh J.J., Lin C.Y. Frequent mutation of Chinese patients with infantile type of GSD II in Taiwan: evidence for a founder effect. Hum. Mutat. 1998; 11(4): 306–12. https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<306::AID-HUMU8>3.0.CO;2-SBecker J.A., Vlach J., Raben N., Nagaraju K., Adams E.M., Hermans M.M., et al. The African origin of the common mutation in African American patients with glycogen-storage disease type II. Am. J. Hum. Genet. 1998; 62(4): 991-4. https://doi.org/10.1086/301788Becker J.A., Vlach J., Raben N., Nagaraju K., Adams E.M., Hermans M.M., et al. The African origin of the common mutation in African American patients with glycogen-storage disease type II. Am. J. Hum. Genet. 1998; 62(4): 991–4. https://doi.org/10.1086/301788Wens S.C., van Gelder C.M., Kruijshaar M.E., de Vries J.M., van der Beek N.A., Reuser A.J., et al. Phenotypical variation within 22 families with Pompe disease. Orphanet J. Rare Dis. 2013; 8: 182. https://doi.org/10.1186/1750-1172-8-182Wens S.C., van Gelder C.M., Kruijshaar M.E., de Vries J.M., van der Beek N.A., Reuser A.J., et al. Phenotypical variation within 22 families with Pompe disease. Orphanet J. Rare Dis. 2013; 8: 182. https://doi.org/10.1186/1750-1172-8-182Smith W., Sullivan-Saarela J.A., Li J.S., Cox G.F., Corzo D., Chen Y.T., et al. Sibling phenotype concordance in classical infantile Pompe disease. Am. J. Med. Genet. 2007; 143(21): 2493- 501. https://doi.org/10.1002/ajmg.a.31936Smith W., Sullivan-Saarela J.A., Li J.S., Cox G.F., Corzo D., Chen Y.T., et al. Sibling phenotype concordance in classical infantile Pompe disease. Am. J. Med. Genet. 2007; 143(21): 2493– 501. https://doi.org/10.1002/ajmg.a.31936Pittis M.G., Donnarumma M., Montalvo A.L., Dominissini S., Kroos M., Rosano C., et al. Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease. Hum. Mutat. 2008; 29(6): E27-E36. https://doi.org/10.1002/humu.20753Pittis M.G., Donnarumma M., Montalvo A.L., Dominissini S., Kroos M., Rosano C., et al. Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease. Hum. Mutat. 2008; 29(6): E27–E36. https://doi.org/10.1002/humu.20753Pittis M.G., Filocamo M. Molecular genetics of late onset glycogen storage disease II in Italy. Acta Myol. 2007; 26(1): 67-71.Pittis M.G., Filocamo M. Molecular genetics of late onset glycogen storage disease II in Italy. Acta Myol. 2007; 26(1): 67–71.De Filippi P., Saeidi K., Ravaglia S., Dardis A., Angelini C., Mongini T., et al. Genotype-phenotype correlation in Pompe disease, a step forward. Orphanet J. Rare Dis. 2014; (9): 102. https://doi.org/10.1186/s13023-014-0102-zDe Filippi P., Saeidi K., Ravaglia S., Dardis A., Angelini C., Mongini T., et al. Genotype-phenotype correlation in Pompe disease, a step forward. Orphanet J. Rare Dis. 2014; (9): 102. https://doi.org/10.1186/s13023-014-0102-zRemiche G., Ronchi D., Magri F., Lamperti C., Bordoni A., Moggio M., et al. Extended phenotype description and new molecular findings in late onset glycogen storage disease type II: a northern Italy population study and review of the literature. J. Neurol. 2014; 261(1): 83-97. https://doi.org/10.1007/s00415-013-7137-2Remiche G., Ronchi D., Magri F., Lamperti C., Bordoni A., Moggio M., et al. Extended phenotype description and new molecular findings in late onset glycogen storage disease type II: a northern Italy population study and review of the literature. J. Neurol. 2014; 261(1): 83–97. https://doi.org/10.1007/s00415-013-7137-2Kroos M., Pomponio R.J., van Vliet L., Palmer R.E., Phipps M., Van der Helm R., et al. Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum. Mutat. 2008; 29(6): 13-26. https://doi.org/10.1002/humu.20745Kroos M., Pomponio R.J., van Vliet L., Palmer R.E., Phipps M., Van der Helm R., et al. Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum. Mutat. 2008; 29(6): 13–26. https://doi.org/10.1002/humu.20745Tajima Y., Matsuzawa F., Aikawa S.I., Okumiya T., Yoshimizu M., Tsukimura T., et al. Structural and biochemical studies on Pompe disease and a “pseudodeficiency of acid α-glucosidase”. J. Hum. Genet. 2007; 52(11): 898-906. https://doi.org/10.1007/s10038-007-0191-9Tajima Y., Matsuzawa F., Aikawa S.I., Okumiya T., Yoshimizu M., Tsukimura T., et al. Structural and biochemical studies on Pompe disease and a “pseudodeficiency of acid α-glucosidase”. J. Hum. Genet. 2007; 52(11): 898–906. https://doi.org/10.1007/s10038-007-0191-9Kumamoto S., Katafuchi T., Nakamura K., Endo F., Oda E., Okuyama T., et al. High frequency of acid α-glucosidase pseudodeficiency complicates newborn screening for glycogen storage disease type II in the Japanese population. Mol. Genet. Metab. 2009; 97(3): 190-5. https://doi.org/10.1016/j.ymgme.2009.03.004Kumamoto S., Katafuchi T., Nakamura K., Endo F., Oda E., Okuyama T., et al. High frequency of acid α-glucosidase pseudodeficiency complicates newborn screening for glycogen storage disease type II in the Japanese population. Mol. Genet. Metab. 2009; 97(3): 190–5. https://doi.org/10.1016/j.ymgme.2009.03.004Kishnani P.S., Nicolino M., Voit T., Rogers R.C., Tsai A.C., Waterson J., et al. Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in Infantile-onset Pompe disease. J. Pediatr. 2006; 149(1): 89-97. https://doi.org/10.1016/j.jpeds.2006.02.035Kishnani P.S., Nicolino M., Voit T., Rogers R.C., Tsai A.C., Waterson J., et al. Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in Infantile-onset Pompe disease. J. Pediatr. 2006; 149(1): 89–97. https://doi.org/10.1016/j.jpeds.2006.02.035De Jesus V.R., Zhang X.K., Keutzer J., Bodamer O.A., Mühl A., Orsini J.J., et al. Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders. Clin. Chem. 2009; 55(1): 158-64. https://doi.org/10.1373/clinchem.2008.111864De Jesus V.R., Zhang X.K., Keutzer J., Bodamer O.A., Mühl A., Orsini J.J., et al. Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders. Clin. Chem. 2009; 55(1): 158–64. https://doi.org/10.1373/clinchem.2008.111864Bodamer O.A., Scott C.R., Giugliani R.; Pompe Disease Newborn Screening Working Group. Newborn screening for Pompe disease. Pediatrics. 2017; 140(Suppl. 1): S4-S13. https://doi.org/10.1542/peds.2016-0280CBodamer O.A., Scott C.R., Giugliani R.; Pompe Disease Newborn Screening Working Group. Newborn screening for Pompe disease. Pediatrics. 2017; 140(Suppl. 1): S4–S13. https://doi.org/10.1542/peds.2016-0280CScott C.R., Elliott S., Buroker N., Thomas L.I., Keutzer J., Glass M., 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. https://doi.org/10.1016/j.jpeds.2013.01.031Scott C.R., Elliott S., Buroker N., Thomas L.I., Keutzer J., Glass M., 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. https://doi.org/10.1016/j.jpeds.2013.01.031QIAGEN. QIAamp® DNA Mini and Blood Mini Handbook; 2016. Available at: https://www.qiagen.com/ch/resources/download.aspx?id=62a200d6-faf4-469b-b50f-2b59cf738962&lang=enQIAGEN. QIAamp® DNA Mini and Blood Mini Handbook; 2016. Available at: https://www.qiagen.com./ch/resources/download.aspx?id= 62a200d6-faf4-469b-b50f-2b59cf738962&lang=enGreen M.R., Sambrook J. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Laboratory; 2012.Green M.R., Sambrook J. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Laboratory; 2012.Primer-BLAST: A tool for finding specific primers. Available at: https://www.ncbi.nlm.nih.gov/tools/primer-blastPrimer-BLAST: A tool for finding specific primers. Available at: https://www.ncbi.nlm.nih.gov/tools/primer-blastThermo Fisher Scientific. Available at: https://www.thermofisher.comThermo Fisher Scientific. Available at: https://www.thermofisher.comNational Center for Biotechnology Information (NCBI). Available at: https://www.ncbi.nlm.nih.govNational Center for Biotechnology Information (NCBI). Available at: https://www.ncbi.nlm.nih.govMRC-Holland. Available at: http://www.mlpa.comMRC-Holland. Available at: http://www.mlpa.comGenome Aggregation Database (gnomAD). Available at: https://gnomad.broadinstitute.orgGenome Aggregation Database (gnomAD). Available at: https://gnomad.broadinstitute.orgGenBank Accession. Available at: https://www.ncbi.nlm.nih.gov/gene/GenBank Accession. Available at: https://www.ncbi.nlm.nih.gov/gene/Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б., Коновалов Ф.А., Масленников А.Б., Степанов В.А. и др. Руководство по интерпретации данных последовательности ДНК человека, полученных методами массового параллельного секвенирования (MPS) (редакция 2018, версия 2). Медицинская генетика. 2019; 18(2): 3-23. https://doi.org/10.25557/2073-7998.2019.02.3-23Ryzhkova O.P., Kardymon O.L., Prokhorchuk E.B., Konovalov F.A., Maslennikov A.B., Stepanov V.A., et al. Guidelines for the interpretation of massive parallel sequencing variants (update 2018, v2). Medi­tsinskaya genetika. 2019; 18(2): 3–23. https://doi.org/10.25557/2073-7998.2019.02.3-23 (in Russian)Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015; 17(5): 405-24. https://doi.org/10.1038/gim.2015.30Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015; 17(5): 405–24. https://doi.org/10.1038/gim.2015.30Human Genome Variation Society (HGVS). Available at: http://www.hgvs.org/Human Genome Variation Society (HGVS). Available at: http://www.hgvs.org/Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета программ Statistica. М.: Медиа Сфера; 2006.Rebrova O.Yu. Statistical Analysis of Medical Data. Application of the Statistica Software Package [Statisticheskiy analiz meditsinskikh dannykh. Primenenie paketa programm Statistica]. Moscow: Media Sfera; 2006. (in Russian)Griner P.F., Mayewski R.J., Mushlin A.I., Greenland P. Selection and interpretation of diagnostic tests and procedures. Principles and applications. Ann. Intern. Med. 1981; 94(4 Pt. 2): 557-92.Griner P.F., Mayewski R.J., Mushlin A.I., Greenland P. Selection and interpretation of diagnostic tests and procedures. Principles and applications. Ann. Intern. Med. 1981; 94(4 Pt. 2): 557–92.Бююль А., Цёфель П. SPSS: Искусство обработки информации. Анализ статистических данных и восстановление скрытых закономерностей. Пер. с нем. СПб.: ДиаСофтЮп; 2005.Achim Bühl, Peter Zöfel. SPSS Version 10. Einführung in die moderne Datenanalyse unter Windows [SPSS: The Art of Information Processing. Statistical Data Analysis and Recovery of Hidden Patterns]. München: Addiwon-Wesley; 2000. (in German)R: The R Project for Statistical Computing. Available at: https://www.r-project.org/.R: The R Project for Statistical Computing. Available at: https://www.r-project.orgHorn P.S., Pesce A.J. Reference intervals: an update. Review. Clin. Chim. Acta. 2003; 334(1-2): 5-23. https://doi.org/10.1016/s0009-8981(03)00133-5Horn P.S., Pesce A.J. Reference intervals: an update. Review. Clin. Chim. Acta. 2003; 334(1-2): 5–23. https://doi.org/10.1016/s0009-8981(03)00133-5Mashima R., Okuyama T. Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles. Mol. Genet. Metab. Rep. 2017; (12): 110-4. https://doi.org/10.1016/j.ymgmr.2017.06.007Mashima R., Okuyama T. Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles. Mol. Genet. Metab. Rep. 2017; (12): 110–4. https://doi.org/10.1016/j.ymgmr.2017.06.007Fukuhara Y., Fuji N., Yamazaki N., Hirakiyama A., Kamioka T., Seo J.H., et al. A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan. Mol. Genet. Metab. Rep. 2018; (14): 3-9. https://doi.org/10.1016/j.ymgmr.2017.10.009Fukuhara Y., Fuji N., Yamazaki N., Hirakiyama A., Kamioka T., Seo J.H., et al. A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan. Mol. Genet. Metab. Rep. 2018; (14): 3–9. https://doi.org/10.1016/j.ymgmr.2017.10.009Kim M.S., Song A., Im M., Huh J., Kang I.S., Song J., et al. Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center. Korean J. Pediatr. 2019; 62(6): 224-34. https://doi.org/10.3345/kjp.2018.06968Kim M.S., Song A., Im M., Huh J., Kang I.S., Song J., et al. Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center. Korean J. Pediatr. 2019; 62(6): 224–34. https://doi.org/10.3345/kjp.2018.06968Oba-Shinjo S.M., da Silva R., Andrade F.G., Palmer R.E., Pomponio R.J., Ciociola K.M., et al. Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations. J. Neurol. 2009; 256(11): 1881-90. https://doi.org/10.1007/s00415-009-5219-yOba-Shinjo S.M., da Silva R., Andrade F.G., Palmer R.E., Pomponio R.J., Ciociola K.M., et al. Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations. J. Neurol. 2009; 256(11): 1881–90. https://doi.org/10.1007/s00415-009-5219-yLöscher W.N., Huemer M., Stulnig T.M., Simschitz P., Iglseder S., Eggers C., et al. Pompe disease in Austria: clinical, genetic and epidemiological aspects. J. Neurol. 2018; 265(1): 159-64. https://doi.org/10.1007/s00415-017-8686-6Löscher W.N., Huemer M., Stulnig T.M., Simschitz P., Iglseder S., Eggers C., et al. Pompe disease in Austria: clinical, genetic and epidemiological aspects. J. Neurol. 2018; 265(1): 159–64. https://doi.org/10.1007/s00415-017-8686-6Hagemans M.L., Winkel L.P., Van Doorn P.A., Hop W.J., Loonen M.C., Reuser A.J., et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain. 2005; 128 (Pt. 3): 671-7. https://doi.org/10.1093/brain/awh384Hagemans M.L., Winkel L.P., Van Doorn P.A., Hop W.J., Loonen M.C., Reuser A.J., et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain. 2005; 128(Pt. 3): 671–7. https://doi.org/10.1093/brain/awh384Niño M.Y., In’t Groen S.L.M., Bergsma A.J., van der Beek N.A.M.E., Kroos M., Hoogeveen-Westerveld M., et al. Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Hum. Mutat. 2019; 40(11): 1954-67. https://doi.org/10.1002/humu.23854Niño M.Y., In’t Groen S.L.M., Bergsma A.J., van der Beek N.A.M.E., Kroos M., Hoogeveen-Westerveld M., et al. Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Hum. Mutat. 2019; 40(11): 1954–67. https://doi.org/10.1002/humu.23854Chen X., Liu T., Huang M., Wu J., Zhu J., Guo Y., et al. Clinical and molecular characterization of infantile-onset Pompe disease in Mainland Chinese patients: identification of two common mutations. Genet. Test. Mol. Biomarkers. 2017; 21(6): 391-6. https://doi.org/10.1089/gtmb.2016.0424Chen X., Liu T., Huang M., Wu J., Zhu J., Guo Y., et al. Clinical and molecular characterization of infantile-onset Pompe disease in Mainland Chinese patients: identification of two common mutations. Genet. Test. Mol. Biomarkers. 2017; 21(6): 391–6. https://doi.org/10.1089/gtmb.2016.0424Labrousse P., Chien Y.H., Pomponio R.J., Keutzer J., Lee N.C., Akmaev V.R., et al. Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program. Mol. Genet. Metab. 2010; 99(4): 379-83. https://doi.org/10.1016/j.ymgme.2009.12.014Labrousse P., Chien Y.H., Pomponio R.J., Keutzer J., Lee N.C., Akmaev V.R., et al. Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program. Mol. Genet. Metab. 2010; 99(4): 379–83. https://doi.org/10.1016/j.ymgme.2009.12.014Kostera-Pruszczyk A., Opuchlik A., Lugowska A., Nadaj A., Bojakowski J., Tylki-Szymanska A., et al. Juvenile onset acid maltase deficiency presenting as a rigid spine syndrome. Neuromuscul. Disord. 2006; 16(4): 282-5. https://doi.org/10.1016/j.nmd.2006.02.001Kostera-Pruszczyk A., Opuchlik A., Lugowska A., Nadaj A., Bojakowski J., Tylki-Szymanska A., et al. Juvenile onset acid maltase deficiency presenting as a rigid spine syndrome. Neuromuscul. Disord. 2006; 16(4): 282–5. https://doi.org/10.1016/j.nmd.2006.02.001Pompe disease GAA variant database (ErasmusMC Rotterdam). Available at: http://www.pompevariantdatabase.nl/pompe_mutations_list.php?qs=c.1856G%3EA&criteria=or&orderby=aMut_ID1Pompe disease GAA variant database (ErasmusMC Rotterdam). Available at: http://www.pompevariantdatabase.nl/pompe_mutations_list.php?qs=c.1856G%3EA&criteria=or&orderby=aMut_ID1Pompe disease GAA variant database (ErasmusMC Rotterdam). Available at: http://www.pompevariantdatabase.nl/pompe_mutations_list.php?qs=c.307T%3EG&criteria=or&orderby=aMut_ID1Pompe disease GAA variant database (ErasmusMC Rotterdam). Available at: http://www.pompevariantdatabase.nl/pompe_mutations_list.php?qs=c.307T%3EG&criteria=or&orderby=aMut_ID1Семячкина А.Н., Сухоруков В.С., Букина Т.М., Яблонская М.И., Меркурьева Е.С., Харабадзе М.Н. и др. Болезнь накопления гликогена, тип II (болезнь Помпе) у детей. Российский вестник перинатологии и педиатрии. 2014; 59(4): 48-55.Semyachkina A.N., Sukhorukov V.S., Bukina T.M., Yablonskaya M.I., Merkur’eva E.S., Kharabadze M.N., et al. Glycogen storage disease, type II (Pompe disease) in children. Rossiyskiy vestnik perinatologii i pediatrii. 2014; 59(4): 48–55. (in Russian)Hermans M.M., van Leenen D., Kroos M.A., Beesley C.E., Van Der Ploeg A.T., Sakuraba H., et al. Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. Hum. Mutat. 2004; 23(1): 47-56. https://doi.org/10.1002/humu.10286Hermans M.M., van Leenen D., Kroos M.A., Beesley C.E., Van Der Ploeg A.T., Sakuraba H., et al. Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. Hum. Mutat. 2004; 23(1): 47–56. https://doi.org/10.1002/humu.10286

The authors declare that there are no conflicts of interest present.