{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:31:41Z","timestamp":1790098301180,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pompe disease (PD) is an autosomal recessive disorder by a deficiency of acid \u03b1\u2010glucosidase (GAA) with intralysosomal glycogen accumulation in multiple tissues. We present the case of a 5\u2010month\u2010old male with hypertrophic cardiomyopathy, hypotony, feeding difficulties, and oxygen requirement since birth. At 3 months of age, he develops heart failure, respiratory impairment, and neurological deterioration. The echocardiogram revealed concentric hypertrophic cardiomyopathy with left\u2010diastolic dysfunction. We found increased creatine\u2010phosphokinase, lactate dehydrogenase, and urinary glucose tetrasaccharide levels, 50% of PAS\u2010positive vacuolated lymphocytes in the peripheral blood smear, and low GAA activity. Sequencing of coding exons and flanking intronic sequences revealed a novel homozygous 4\u00a0bp deletion in exon 15 of the <jats:italic>GAA<\/jats:italic> gene (c.2066_2069delAGCC\/p.Glu689Glyfs*6). IOPD was diagnosed. At 5 months old, we started enzyme replacement therapy with an alpha\u2010alglucosidase of 20\u2009mg\/kg weekly and immunomodulation with intravenous immunoglobulin. He developed two cardiorespiratory arrests with subsequent neurologic deterioration, convulsive crisis, and respiratory failure and died at 9 months old. We found the usual PD hallmarks in the heart, striated muscle, and liver but also we found neuronal lesions characterized by cytoplasm vacuolization with PAS\u2010positive granules in the central nervous system and myenteric plexus. We describe a novel <jats:italic>GAA<\/jats:italic> gene pathogenic variant with a particular phenotype characterized by classic IOPD and neurologic histopathological findings. Enhancing the knowledge of lysosomal diseases is critical to improving the diagnosis and treatment of these patients.<\/jats:p>","DOI":"10.1002\/mgg3.1957","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T12:36:36Z","timestamp":1652099796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Classic infantile\u2010onset Pompe disease with histopathological neurologic findings linked to a novel <i>GAA<\/i> gene 4\u00a0bp deletion: A case study"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-585X","authenticated-orcid":false,"given":"Magdalena","family":"Cer\u00f3n\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Lysosomal Diseases Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Castillo\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Lysosomal Diseases Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos\u2010Patricio","family":"Acosta\u2010Rodr\u00edguez\u2010Bueno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Aguirre\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics, Genetics and Bioinformatics, Department of Genetics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan\u2010Rafael","family":"Murillo\u2010Eliosa","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Valencia\u2010Mayoral","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argelia","family":"Escobar\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-1047","authenticated-orcid":false,"given":"Juan\u2010Luis","family":"Salgado\u2010Loza","sequence":"additional","affiliation":[{"name":"Scientific Information Department SICODIC  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.12816\/0003308"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067052"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/301788"},{"key":"e_1_2_9_5_1","volume-title":"MacSween's pathology of the liver","author":"Burt A.","year":"2017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.05.56"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000233014.84318.4e"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.05.27"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.04.70"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(1998)11:3<209::AID\u2010HUMU5>3.0.CO;2\u2010C"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7811"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20107\u201035"},{"key":"e_1_2_9_14_1","first-page":"3389","volume-title":"The metabolic and molecular bases of inherited disease","author":"Hirschhorn R.","year":"2001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20101809.1996.tb00433.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_192"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.08.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.11.033"},{"key":"e_1_2_9_20_1","first-page":"147","volume-title":"Stocker and Dehner pediatric pathology","author":"Koo S. 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