Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes
Abstract Background Pompe disease is a rare genetic disorder caused by a deficiency of the enzyme acid alpha-glucosidase. This condition leads to muscle weakness, respiratory problems, and heart abnormalities in affected individuals. Methods The aim of the study is to share our experience through cr...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Italian Journal of Pediatrics |
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| Online Access: | https://doi.org/10.1186/s13052-025-01837-8 |
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| author | Mohamed Abdelghafar Hussein Heba ElTaher Ranim Mahmoud Donia Sobh Mohammad Al-Haggar |
| author_facet | Mohamed Abdelghafar Hussein Heba ElTaher Ranim Mahmoud Donia Sobh Mohammad Al-Haggar |
| author_sort | Mohamed Abdelghafar Hussein |
| collection | DOAJ |
| description | Abstract Background Pompe disease is a rare genetic disorder caused by a deficiency of the enzyme acid alpha-glucosidase. This condition leads to muscle weakness, respiratory problems, and heart abnormalities in affected individuals. Methods The aim of the study is to share our experience through cross sectional study of patients with infantile-onset Pompe disease (IOPD) with different genetic variations, resulting in diverse clinical presentations. We evaluated their phenotype, genotype, radiological and laboratory findings including their cross-reactive immunologic material (CRIM) status. Infantile Pompe disease was diagnosed by measurement of the activity of the enzyme alpha-glucosidase. The diagnosis was confirmed by molecular genetic testing using PCR amplification and sequencing of the acid alpha-glucosidase (GAA) gene. Routine two-D echocardiography, and multi-parametric ECG-gated cardiac magnetic resonance imaging (CMR) were done to patients six months after starting enzyme replacement therapy (ERT). Results The results of our study revealed different genetic mutations among our patients, different CRIM status and also CMR abnormalities. CMR imaging revealed abnormalities in all cases that underwent the procedure, including myocardial and vascular changes, with feature tracking indicating issues across all parameters and LGE suggesting fibrosis. The patient with a positive immune response had the most severe cardiac abnormalities, despite improvements in muscle weakness and motor skills from ERT. This underscores that delayed diagnosis and ERT can lead to irreversible heart damage from autophagy buildup. Conclusion Pompe disease has various clinical presentations and results in significant CMR findings, which can be attributed to different genetic mutations. Early initiation of enzyme replacement therapy in infantile-onset Pompe disease is important to maximize its benefits. |
| format | Article |
| id | doaj-art-adc7fe699157451abd9c8f009f687977 |
| institution | Kabale University |
| issn | 1824-7288 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Italian Journal of Pediatrics |
| spelling | doaj-art-adc7fe699157451abd9c8f009f6879772025-01-26T12:45:14ZengBMCItalian Journal of Pediatrics1824-72882025-01-015111810.1186/s13052-025-01837-8Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomesMohamed Abdelghafar Hussein0Heba ElTaher1Ranim Mahmoud2Donia Sobh3Mohammad Al-Haggar4Pediatrics Department, faculty of medicine, Kafrelsheikh UniversityPediatrics Department, Genetics Unit, Mansoura UniversityPediatrics Department, Genetics Unit, Mansoura UniversityRadiodiagnosis Department, Mansoura UniversityPediatrics Department, Genetics Unit, Mansoura UniversityAbstract Background Pompe disease is a rare genetic disorder caused by a deficiency of the enzyme acid alpha-glucosidase. This condition leads to muscle weakness, respiratory problems, and heart abnormalities in affected individuals. Methods The aim of the study is to share our experience through cross sectional study of patients with infantile-onset Pompe disease (IOPD) with different genetic variations, resulting in diverse clinical presentations. We evaluated their phenotype, genotype, radiological and laboratory findings including their cross-reactive immunologic material (CRIM) status. Infantile Pompe disease was diagnosed by measurement of the activity of the enzyme alpha-glucosidase. The diagnosis was confirmed by molecular genetic testing using PCR amplification and sequencing of the acid alpha-glucosidase (GAA) gene. Routine two-D echocardiography, and multi-parametric ECG-gated cardiac magnetic resonance imaging (CMR) were done to patients six months after starting enzyme replacement therapy (ERT). Results The results of our study revealed different genetic mutations among our patients, different CRIM status and also CMR abnormalities. CMR imaging revealed abnormalities in all cases that underwent the procedure, including myocardial and vascular changes, with feature tracking indicating issues across all parameters and LGE suggesting fibrosis. The patient with a positive immune response had the most severe cardiac abnormalities, despite improvements in muscle weakness and motor skills from ERT. This underscores that delayed diagnosis and ERT can lead to irreversible heart damage from autophagy buildup. Conclusion Pompe disease has various clinical presentations and results in significant CMR findings, which can be attributed to different genetic mutations. Early initiation of enzyme replacement therapy in infantile-onset Pompe disease is important to maximize its benefits.https://doi.org/10.1186/s13052-025-01837-8Pompe diseaseGenotypesCardiac magnetic resonance imaging (CMR)ERT |
| spellingShingle | Mohamed Abdelghafar Hussein Heba ElTaher Ranim Mahmoud Donia Sobh Mohammad Al-Haggar Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes Italian Journal of Pediatrics Pompe disease Genotypes Cardiac magnetic resonance imaging (CMR) ERT |
| title | Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes |
| title_full | Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes |
| title_fullStr | Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes |
| title_full_unstemmed | Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes |
| title_short | Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes |
| title_sort | clinical manifestations in egyptian pompe disease patients molecular variability and enzyme replacement therapy ert outcomes |
| topic | Pompe disease Genotypes Cardiac magnetic resonance imaging (CMR) ERT |
| url | https://doi.org/10.1186/s13052-025-01837-8 |
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