Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction
Glycogen storage disease II or Pompe disease (PD), is a rare autosomal recessive disorder due to biallelic pathogenic variants in GAA, resulting in the enzymatic deficiency of alpha-1,4-glucosidase. Two clinical forms are recognized, namely, early onset (EOPD) and late-onset (LOPD). We present the c...
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Frontiers Media S.A.
2025-06-01
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| author | Monica Sciacco Sabrina Lucchiari Letizia Bertolasi Giacomo Pietro Comi Giacomo Pietro Comi Stefania Corti Stefania Corti Dario Ronchi Dario Ronchi |
| author_facet | Monica Sciacco Sabrina Lucchiari Letizia Bertolasi Giacomo Pietro Comi Giacomo Pietro Comi Stefania Corti Stefania Corti Dario Ronchi Dario Ronchi |
| author_sort | Monica Sciacco |
| collection | DOAJ |
| description | Glycogen storage disease II or Pompe disease (PD), is a rare autosomal recessive disorder due to biallelic pathogenic variants in GAA, resulting in the enzymatic deficiency of alpha-1,4-glucosidase. Two clinical forms are recognized, namely, early onset (EOPD) and late-onset (LOPD). We present the case of an asymptomatic 33-year-old man who underwent a genetic screening for autosomal recessive disorders (parental prenatal counselling) and was found to carry the homozygous pathogenic GAA substitution NM_000152.5(GAA):c.-32-13T>G (IVS1). Neurological examination, serum CK levels, electromyography, muscle MRI, respiratory and cardiac screening were reported normal. We investigated the effects of the variant at transcript and protein levels in available tissues from the proband and his parents. The IVS1-32-13T>G variant (dbSNP: rs386834236, Clin Var ID: 4,027) occurs in 90% of Caucasian LOPD patients and is associated with a broad range of symptom onset. About 50 subjects have been reported harboring this variant in homozygosis and most of them are asymptomatic, although a subset develops symptoms with time. Residual levels of alpha-1,4-glucosidase activity and protein content do not seem to reflect clinical severity in homozygous IVS1 LOPD patients. |
| format | Article |
| id | doaj-art-d18b4e686a9a4deb976d0e0028d12316 |
| institution | OA Journals |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-d18b4e686a9a4deb976d0e0028d123162025-08-20T02:10:23ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-06-011610.3389/fgene.2025.15743811574381Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunctionMonica Sciacco0Sabrina Lucchiari1Letizia Bertolasi2Giacomo Pietro Comi3Giacomo Pietro Comi4Stefania Corti5Stefania Corti6Dario Ronchi7Dario Ronchi8Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyNeurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyNeuromuscular and Rare Disease Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, ItalyNeurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyGlycogen storage disease II or Pompe disease (PD), is a rare autosomal recessive disorder due to biallelic pathogenic variants in GAA, resulting in the enzymatic deficiency of alpha-1,4-glucosidase. Two clinical forms are recognized, namely, early onset (EOPD) and late-onset (LOPD). We present the case of an asymptomatic 33-year-old man who underwent a genetic screening for autosomal recessive disorders (parental prenatal counselling) and was found to carry the homozygous pathogenic GAA substitution NM_000152.5(GAA):c.-32-13T>G (IVS1). Neurological examination, serum CK levels, electromyography, muscle MRI, respiratory and cardiac screening were reported normal. We investigated the effects of the variant at transcript and protein levels in available tissues from the proband and his parents. The IVS1-32-13T>G variant (dbSNP: rs386834236, Clin Var ID: 4,027) occurs in 90% of Caucasian LOPD patients and is associated with a broad range of symptom onset. About 50 subjects have been reported harboring this variant in homozygosis and most of them are asymptomatic, although a subset develops symptoms with time. Residual levels of alpha-1,4-glucosidase activity and protein content do not seem to reflect clinical severity in homozygous IVS1 LOPD patients.https://www.frontiersin.org/articles/10.3389/fgene.2025.1574381/fullPompe diseaseGAAmuscle glycogenosisIVS1-32-13T>Gacid maltase deficiency |
| spellingShingle | Monica Sciacco Sabrina Lucchiari Letizia Bertolasi Giacomo Pietro Comi Giacomo Pietro Comi Stefania Corti Stefania Corti Dario Ronchi Dario Ronchi Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction Frontiers in Genetics Pompe disease GAA muscle glycogenosis IVS1-32-13T>G acid maltase deficiency |
| title | Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| title_full | Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| title_fullStr | Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| title_full_unstemmed | Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| title_short | Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| title_sort | case report incidental late onset pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction |
| topic | Pompe disease GAA muscle glycogenosis IVS1-32-13T>G acid maltase deficiency |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1574381/full |
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