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Early Cardiac Changes in Children with Anderson–Fabry Disease

  • Research Report
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JIMD Reports - Volume 11

Part of the book series: JIMD Reports ((JIMD,volume 11))

Abstract

Objective: Limited evidence is available about the early cardiac manifestation of Fabry disease (FD) in children. We aimed to evaluate cardiac involvement in children with FD by analysing serial structural and electrocardiographic changes.

Methods: The data were acquired from 22 children with FD [11 males; median age 9.8 (ranging 2.5–16) years]. Seven patients (5 males) were on enzyme replacement therapy (ERT) with Agalasidase alpha. Echocardiography, ECG and 24-h ECG monitoring recordings were acquired during routine annual clinical controls. ECG data were compared to a group of age-and gender-matched controls.

Results: At baseline, ECG and ECHO parameters of left ventricular mass were similar in both males and females. Three boys (all were on ERT) developed left ventricular hypertrophy (LVH) during two-year follow-up. The progression to LVH was accompanied by the appearance of frequent ventricular premature beats in two cases and supraventricular premature beats (SPBs) with T wave inversion in one case. T wave inversion and SPBs were detected in two younger relatives of a patient with LVH, in the absence of detectable LVH. Seven out of 22 patients had T wave abnormalities. Five of them were males (p = 0.03) all carrying the N215S mutation (p = 0.03). At baseline, median PR intervals were prolonged in FD subjects compared to controls [143 (122–177) vs. 122 (82–165) ms; p < 0.0001].

Conclusions: Cardiac complications of FD become apparent in childhood as subtle changes with slow but detectable progression over time, with males more frequently affected than females. Progression of LVH was apparent in three children despite ERT.

Competing interests: None declared

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Abbreviations

AVB:

AV block

ECHO:

Echocardiography

ERT:

Enzyme replacement therapy

FD:

Fabry disease

Holter ECG:

24-h ECG monitoring

HR:

Heart rate

LV:

Left ventricle

LVH:

Left ventricular hypertrophy

M:

Month

SPBs:

Supraventricular premature beats

UR:

Uma Ramaswami

VPBs:

Ventricular premature beats

Y:

Year

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Acknowledgements

We thank the metabolic nurses and the cardiology technicians at Addenbrooke’s Hospital for their help with collating data and performing cardiac ECHO and Holter monitoring.

Author information

Authors and Affiliations

  1. Department of Medicine – Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic

    Stepan Havranek & Ales Linhart

  2. Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic

    Zuzana Urbanova

  3. Willink Biochemical Genetics Unit, Central Manchester University Hospitals, NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK

    Uma Ramaswami

Authors
  1. Stepan Havranek
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  2. Ales Linhart
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  3. Zuzana Urbanova
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  4. Uma Ramaswami
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Corresponding author

Correspondence to Uma Ramaswami .

Editor information

Editors and Affiliations

  1. Medizinische Universität Innsbruck Sektionen für Humangenetik und Klinische, Innsbruck, Austria

    Johannes Zschocke

  2. Clinical Pharmacology Unit, Division of Health Sciences Washington State University, Spokane, Washington, USA

    K Michael Gibson

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, United Kingdom

    Garry Brown

  4. Department of Pediatrics IGMD, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Eva Morava

  5. Center for Child and Adolescent Medicine Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Verena Peters

Appendices

Synopsis

Early changes in ECG/Holter ECG and echocardiography related to cardiac involvement caused by Fabry disease can be observed in children, both males and females.

Details of the Contributions of Individual Authors

  • Stepan Havranek: analysis and interpretation of data; drafting of manuscript

  • Ales Linhart: analysis and interpretation of data; revising article critically for important intellectual content

  • Zuzana Urbanova: analysis of data; revising article critically for important intellectual content

  • Uma Ramaswami: Developing concept, design of study, patient follow-up, data collection; revising article critically for important intellectual content

Guarantor Author

Dr. Uma Ramaswami MD, FRCPCH.

Funding

Supported by Program for research development in Charles University: PRVOUK-P35/LF1/5.

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Details of Ethics Approval

The study was approved by Norfolk Research Ethics Committee. Reference number: 11/H0310/4.

Disclosure

None declared.

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Havranek, S., Linhart, A., Urbanova, Z., Ramaswami, U. (2013). Early Cardiac Changes in Children with Anderson–Fabry Disease. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 11. JIMD Reports, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_222

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  • DOI: https://doi.org/10.1007/8904_2013_222

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  • Print ISBN: 978-3-642-37327-5

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