{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:34:22Z","timestamp":1791462862648,"version":"4.3.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic \u03b1-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>Case 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480\u223c11,880 U\/L) and low GAA activity (2.72 nmol\/1 h\/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C &amp;gt; T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G &amp;gt; A, p. Gly576Ser and c.2065G &amp;gt; A, p. Glu689Lys), which were believed to induce the patient\u2019s low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408\u223c24,828 U\/L). His blood GAA activity (colorimetric method) was 9.02 nmol\/1 h\/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.855510","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T12:17:51Z","timestamp":1654085871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Duchenne Muscular Dystrophy With Low Acidic \u03b1-Glucosidase Activity: Two Case Reports and Literature Review"],"prefix":"10.3389","volume":"10","author":[{"given":"Xiufang","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuandi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuese","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Ba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youzhen","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/s1474-4422(18)30024-3","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management.","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/s0140-6736(08)61555-x","article-title":"Pompe\u2019s disease.","volume":"372","author":"van der Ploeg","year":"2008","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.ymgme.2009.12.014","article-title":"Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program.","volume":"99","author":"Labrousse","year":"2010","journal-title":"Mol Genet Metab."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy.","volume":"7","author":"Duan","year":"2021","journal-title":"Nat Rev Dis Primers."},{"key":"B5","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1007\/s10038-007-0191-9","article-title":"Structural and biochemical studies on Pompe disease and a \u201cpseudodeficiency of acid alpha-glucosidase\u201d.","volume":"52","author":"Tajima","year":"2007","journal-title":"J Hum Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s10038-019-0603-7","article-title":"Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients.","volume":"64","author":"Momosaki","year":"2019","journal-title":"J Hum Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1469-1809.1982.tb00700.x","article-title":"Extension of human acid alpha-glucosidase polymorphism by isoelectric focusing in polyacrylamide gel.","volume":"46","author":"Nickel","year":"1982","journal-title":"Ann Hum Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/j.1469-1809.1996.tb00433.x","article-title":"Identification of an E689K substitution as the molecular basis of the human acid alpha-glucosidase type 4 allozyme (GAA*4).","volume":"60","author":"Huie","year":"1996","journal-title":"Ann Hum Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/ejhg.2008.34","article-title":"p.[G576S; 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