Subclinical Myocardial Dysfunction in Children With Wilson's Disease
Assessment of Subtle Myocardial Dysfunction in Children With Wilson's Disease: A Case-Control Study
- Registry ID
- NCT07765472
- Source registry
- NCT
- Status
- ACTIVE_NOT_RECRUITING
- Study type
- OBSERVATIONAL
- Sponsor
- Hebatullah Fawzy
- Enrollment
- 72
- Start date
- 2025-10-01
- Completion date
- 2026-11-30
- Last update
- 2026-08-14
Conditions
- Electrocardiographic Changes
- Wilson's Disease
- Myocardial Dysfunction
- Wilson Disease
- Speckle Tracking Echocardiography
- Children
Summary
Wilson's disease (WD) is one of the most common metabolic liver diseases in older children. The most frequent clinical presentation is liver disease. However, Wilson's disease (WD) is a multisystem disorder. It is concluded that four modes of cardiac manifestations in Wilson's disease (WD) include arrhythmias, cardiomyopathy, cardiac death, and autonomic dysfunction. Such possible cardiac involvement should be added to the clinical picture of Wilson's disease (WD) involving the hepatic and central nervous system(CNS).
The data on cardiac manifestations in children is very limited and only few adult studies are available.
In this study, the investigators aim to unveil subclinical cardiac dysfunction in children with Wilson's disease with apparently normal cardiac functions by conventional assessment.
Detailed description
Wilson's disease (WD) is an autosomal recessive metabolic liver disorder caused by toxic copper accumulation. While hepatic and neurological manifestations are well recognized, copper can also accumulate in cardiac tissue, potentially leading to subtle myocardial changes, arrhythmias, and heart failure. Traditional two-dimensional (2D) echocardiography often appears normal in early stages. This study aims to evaluate early left ventricular (LV) systolic and diastolic dysfunction in pediatric patients with Wilson's disease using speckle tracking echocardiography (STE) and tissue Doppler imaging, and to correlate these findings with serum levels of Pro-Brain Natriuretic Peptide (Pro-BNP) and ceruloplasmin.
Interventions
- DEVICE: Echocardiography
- DEVICE: Electrocardiography
- OTHER: N-terminal pro b- type natriuretic peptide
Inclusion criteria
Inclusion Criteria
1. Confirmed diagnosis of Wilson's disease based on Leipzig scoring criteria (including clinical signs, Kayser-Fleischer rings, low ceruloplasmin, or genetic analysis).
2. Age between 4 years and 18 years.
3. Written informed consent obtained from parents or legal guardians.
Exclusion criteria
Exclusion Criteria
1. Children with clinical evidence of overt heart failure or known congenital heart disease.
2. Children suffering from fulminant hepatitis.
3. Known co-existing primary liver diseases other than Wilson's disease.
4. Presence of syndromic disorders or major congenital anomalies.
Primary outcomes
[{"measure":"Left Ventricular Peak Longitudinal Strain (LV-PLS)","timeFrame":"Baseline (Day 1 , at single cross-sectional evaluation)."}]
Locations
- National Hepatology and Tropical Research Institute (NHTMRI), Giza, Egypt
- Faculty of medicine AinShams U, Cairo, Egypt
Publications
- European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol. 2012 Mar;56(3):671-85. doi: 10.1016/j.jhep.2011.11.007.
- https://ebm.one/en/chapter-table/scoring-system-developed-8th-international-meeting-wilson-disease-leipzig-2001
- https://doi.org/10.1038/s41598-024-59377-w
- European Association for the Study of the Liver. EASL-ERN Clinical Practice Guidelines on Wilson's disease. J Hepatol. 2025 Feb 22:S0168-8278(24)02706-5. doi: 10.1016/j.jhep.2024.11.007. Online ahead of print.
- Quick S, Reuner U, Weidauer M, Hempel C, Heidrich FM, Mues C, Sveric KM, Ibrahim K, Reichmann H, Linke A, Speiser U. Cardiac and autonomic function in patients with Wilson's disease. Orphanet J Rare Dis. 2019 Jan 28;14(1):22. doi: 10.1186/s13023-019-1007-7.
- Ovchinnikova EV, Garbuz MM, Ovchinnikova AA, Kumeiko VV. Epidemiology of Wilson's Disease and Pathogenic Variants of the ATP7B Gene Leading to Diversified Protein Disfunctions. Int J Mol Sci. 2024 Feb 18;25(4):2402. doi: 10.3390/ijms25042402.
- Dang J, Chevalier K, Letavernier E, Tissandier C, Mouawad S, Debray D, Obadia M, Poujois A. Kidney involvement in Wilson's disease: a review of the literature. Clin Kidney J. 2024 Mar 9;17(4):sfae058. doi: 10.1093/ckj/sfae058. eCollection 2024 Apr.
- Romuk E, Jachec W, Zbrojkiewicz E, Mroczek A, Niedziela J, Gasior M, Rozentryt P, Wojciechowska C. Ceruloplasmin, NT-proBNP, and Clinical Data as Risk Factors of Death or Heart Transplantation in a 1-Year Follow-Up of Heart Failure Patients. J Clin Med. 2020 Jan 3;9(1):137. doi: 10.3390/jcm9010137.
- Chevalier K, Benyounes N, Obadia MA, Van Der Vynckt C, Morvan E, Tibi T, Poujois A. Cardiac involvement in Wilson disease: Review of the literature and description of three cases of sudden death. J Inherit Metab Dis. 2021 Sep;44(5):1099-1112. doi: 10.1002/jimd.12418. Epub 2021 Aug 2.
- https://doi.org/10.4236/wjcd.2019.93018
- Salatzki J, Mohr I, Heins J, Cerci MH, Ochs A, Paul O, Riffel J, Andre F, Hirschberg K, Muller-Hennessen M, Giannitsis E, Friedrich MG, Merle U, Weiss KH, Katus HA, Ochs M. The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2021 Jun 24;23(1):84. doi: 10.1186/s12968-021-00760-1.
- Wiernicka A, Dadalski M, Janczyk W, Kaminska D, Naorniakowska M, Husing-Kabar A, Schmidt H, Socha P. Early Onset of Wilson Disease: Diagnostic Challenges. J Pediatr Gastroenterol Nutr. 2017 Nov;65(5):555-560. doi: 10.1097/MPG.0000000000001700.
- Sanchez-Monteagudo A, Ripolles E, Berenguer M, Espinos C. Wilson's Disease: Facing the Challenge of Diagnosing a Rare Disease. Biomedicines. 2021 Aug 28;9(9):1100. doi: 10.3390/biomedicines9091100.
- https://doi.org/10.21608/cupsj.2021.71046.1018
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