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. 2025 Jan 23;51(1):13.
doi: 10.1186/s13052-025-01837-8.

Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes

Mohamed Abdelghafar Hussein  1 , Heba ElTaher  2 , Ranim Mahmoud  2 , Donia Sobh  3 , Mohammad Al-Haggar  2
Affiliations

Clinical manifestations in Egyptian Pompe disease patients: Molecular variability and enzyme replacement therapy (ERT) outcomes

Mohamed Abdelghafar Hussein et al. Ital J Pediatr. .

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.

Keywords: Cardiac magnetic resonance imaging (CMR); ERT; Genotypes; Pompe disease.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All experimental protocols were approved from ethical committee in Mansoura university (IRB number MD.21.01.404). Written Informed consent was obtained from the patients (if above 16) or patient’s legal guardian for participation in the research. All methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication: Informed consent was obtained from the patient’s guardian for their child’s information to be published. Studies involving animals: Not applicable. Conflict of interest: No conflicts of interest or financial conflict.

Figures

Fig. 1
Fig. 1
Case with homozygous p.[Arg702Cys] shows more hypertrophied left ventricle and more LGE (A and C) as compared to male patient with a male infant with homozygous mutation: c.[2560 C > T]; [2560 C > T] and (p.[Arg854Ter]; [Arg854Ter]) (B and D)
Fig. 2
Fig. 2
A: Phase sensitive inversion recovery image in female infant with Pompe disease shows septal late gadolinium enhancement in apical part of left ventricle denoting non ischemic myocardial injury (yellow arrow), B: Late gadolinium enhancement in anteroseptal in apical part of left ventricle myocardium in the same infant (blue arrow), C: Aortic wall enhancement in the same infant in inversion recovery sequence (red arrow)
Fig. 3
Fig. 3
Feature tracking CMR of the same infant shows affection in all strains denoting significant myocardial deformation (A: longitudinal strain, B: Radial strain, C: circumferential strain)
See this image and copyright information in PMC

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References

    1. Kohler L, Puertollano R, Raben N. Pompe disease: from Basic Science to Therapy. Neurotherapeutics. 2018;15(4):928–42. - PMC - PubMed
    1. Wisselaar HA, et al. Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J Biol Chem. 1993;268(3):2223–31. - PubMed
    1. Dasouki M, et al. Pompe disease: literature review and case series. Neurol Clin. 2014;32(3):751–76. ix. - PMC - PubMed
    1. Parini R, et al. Long term clinical history of an Italian cohort of infantile onset pompe disease treated with enzyme replacement therapy. Orphanet J Rare Dis. 2018;13(1):32. - PMC - PubMed
    1. Byrne BJ, et al. Pompe disease: design, methodology, and early findings from the Pompe Registry. Mol Genet Metab. 2011;103(1):1–11. - PubMed

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