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JACC Case Rep
JACC Case Rep
JACC Case Reports
2666-0849
Elsevier

S2666-0849(24)00239-0
10.1016/j.jaccas.2024.102446
102446
Mini-Focus Issue on Congenital Heart Disease
Imaging Vignette: Clinical Vignette
Assessing Gene Therapy Efficacy in Infantile-Onset Pompe Disease
Myocardial Native T1 Values of CMR
Wang Wanbing MS
Zhang Xinghua MD
Lyu Jinhao MD
Yan Fei BS
Lou Xin MD louxin@301hospital.com.cn
∗
Department of Radiology, Chinese PLA General Hospital, Beijing, China
∗ Address for correspondence: Dr Xin Lou, Department of Radiology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100853, China. louxin@301hospital.com.cn
21 8 2024
21 8 2024
21 8 2024
29 16 10244618 4 2024
30 5 2024
12 6 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
We report the novel finding of a widespread reduction in myocardial native T1 values and size of abnormal regions following gene therapy in a pediatric patient with infantile-onset Pompe disease. We emphasize the importance of serial cardiac magnetic resonance in assessing the efficacy of gene therapy and monitoring myocardial alterations in Pompe disease.

Graphical Abstract

Key Words

cardiac magnetic resonance imaging
gene therapy
genetic disorders
glucose metabolism disorders
Abbreviations and Acronyms

AAV adeno-associated virus

CMR cardiac magnetic resonance

ERT enzyme replacement therapy

GAA α-1,4 glucosidase

IOPD infantile-onset Pompe disease
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pmcA 1-year-old male child presented with feeding difficulties, diminished oral intake, retarded weight accretion, and perioral cyanosis accompanied by severe crying since birth. At 3 months, echocardiography revealed myocardial hypertrophy. At 4 months, genetic tests revealed 2 compound heterozygous variants, confirming the diagnosis of infantile-onset Pompe disease (IOPD). The infant started enzyme replacement therapy (ERT) immediately after diagnosis. The child exhibited slow progress in motor skills progress without regression during treatment.

The child was referred to our institution for gene therapy. Physical examinations on admission showed a precordial murmur graded as 2 or 3 of 6, muscular strength rated as IV+ in the upper limbs and V– in the lower limbs, and low muscle strength of the limbs. Cardiac magnetic resonance (CMR) showed severe thickening of the ventricular walls, particularly the interventricular septum, mild hyperkinesia of the left ventricle, and an ejection fraction of 89% (Figures 1A to 1D). Hepatic dysfunction and abnormal myocardial enzyme levels were also noted. Following a comprehensive examination and exclusion of all contraindications, gene therapy was planned. At the 4-month post-treatment follow-up, an improvement in muscle strength from IV+ to V– was evaluated in the upper limbs. Physical and echocardiography examinations were similar to before. Magnetic resonance after 4 months post-treatment showed a diffuse reduction in myocardial native T1 values and the size of abnormal regions (Figures 1E and 1F) with similar ejection fraction (86%).Figure 1 Cardiac Magnetic Resonance in the Pediatric Patient with Infantile-Onset Pompe Disease

T1 mapping images in pre– and post–gene therapy. (A to D) The cine sequence showed wall thickness, particularly the interventricular septum. (F) Post-treatment after 4 months showed a decrease in the native T1 values of the anomalous of the mid anteroseptal wall and the insertion site compared with (E) pretreatment (1,351.69 ms vs 1,294.22 ms, 1,273.31 ms vs 1,218.17 ms). Furthermore, there was a reduction of abnormal regions in size.

Pompe disease is an autosomal recessive disorder characterized by a deficiency of the α-1,4 glucosidase (GAA), leading to glycogen accumulation in target tissues with progressive organ failure. IOPD is particularly severe, with rapid progression and a high mortality rate.1 ERT is currently the standard of care for Pompe disease, but it entails several limitations. Aiming to overcome the limited efficacy of ERT, researchers developed adeno-associated virus (AAV) gene therapy for IOPD patients. AAV-associated gene therapy for IOPD delivers a missing or defective gene to physiologically relevant target tissues, providing a way to prolong the efficacy of GAA enzyme activity. This treatment could improve the GAA enzyme level in the blood, with an excellent safety profile and the high efficiency of transduction of target tissues. However, the modulation of immune responses in gene therapy is not fully understood, and the solutions of neutralizing antibodies remain still lacking.2

CMR offers superior tissue characterization and myocardial detailing compared with echocardiography. Studies have shown that CMR is more reliable and accurate than echocardiography, especially for assessing cardiac structure and function.3

CMR showed a generalized reduction in myocardial native T1 values after gene therapy, consistent with the clinical feature of improved muscle strength. With this consistency, the report presents a novel observation of a generalized reduction in myocardial native T1 values in IOPD patients undergoing effective gene therapy.

This case report presents a comprehensive assessment and management of IOPD, with particular emphasis on the role of CMR in monitoring treatment response. The observed reduction in myocardial native T1 values post–gene therapy suggests a promising avenue for evaluating treatment efficacy and myocardial fibrosis in IOPD patients.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Acknowledgments

The authors are grateful for the support of the entire staff of the Department of Radiology at Chinese PLA General Hospital.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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References

1 Alizadeh Y. Saidi H. Saeedi V. Infantile-onset Pompe disease: a case report emphasizing the role of genetic counseling and prenatal testing BMC Pediatr 24 1 2024 194 38500078
2 Muñoz S. Bertolin J. Jimenez V. Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy Mol Metab 81 2024 101899
3 Habib M. Adler A. Fardfini K. Progression of myocardial fibrosis in hypertrophic cardiomyopathy: a cardiac magnetic resonance study JACC Cardiovasc Imaging 14 5 2021 947 958 33248971
