Subclinical Myocardial Dysfunction in Children With Wilson's Disease

NCT07765472 | Active Not Recruiting

• 1 other identifier: Wilson's disease and Heart
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Wilson's Disease; Myocardial Dysfunction; Children; Wilson Disease; Speckle Tracking Echocardiography; Electrocardiographic Changes

Keywords

WD; pedia; cardiac; childern; LV dysfunction; Wilson; BNP; ceruloplasmin; Speckled tracking; Pro-BNP; STE

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Peak Longitudinal Strain (LV-PLS)

  Left Ventricular Peak Longitudinal Strain (LV-PLS) assessed by Speckle Tracking Echocardiography (STE) to evaluate subclinical LV systolic dysfunction. Expressed as a negative percentage (%), where a less negative percentage indicates impaired function.

  Baseline (Day 1 , at single cross-sectional evaluation).

Secondary Outcomes (4)

• Serum Pro-Brain Natriuretic Peptide (Pro-BNP) Level

  Baseline (Day 1 , at single cross-sectional evaluation).

• Tissue Doppler LV Filling Pressure (E/e' Ratio)

  Baseline (Day 1 , at single cross-sectional evaluation).

• Serum Ceruloplasmin Level Correlation

  Baseline (Day 1,at time of cardiac evaluation or within 6 months preceding cardiac evaluation).

• Frequency of Electrocardiographic (ECG) Abnormalities

  Baseline (Day 1 , at single cross-sectional evaluation).

Study Arms (2)

Group 1 (Cases)

Children aged 4-18 years with confirmed Wilson's disease recruited from the Pediatric Hepatology Clinic at the National Hepatology and Tropical Medicine Research Institute (NHTMRI).

Device: Echocardiography; Device: Electrocardiography; Diagnostic Test: N-terminal pro b- type natriuretic peptide

Group 2 (Controls)

Age- and sex-matched control children without chronic liver or cardiac illness recruited from the outpatient clinic.

Device: Echocardiography

Interventions

Echocardiography DEVICE

a safe, painless test that uses sound waves to create moving pictures of your heart's structure and pumping function.

Also known as: Echo

Group 1 (Cases); Group 2 (Controls)

Electrocardiography DEVICE

a quick, painless test that records the electrical signals in the heart.

Also known as: ECG

Group 1 (Cases)

N-terminal pro b- type natriuretic peptide DIAGNOSTIC_TEST

a protein made by our heart, examined by peripheral blood sample.

Also known as: pro BNP

Group 1 (Cases)

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

They will be divided in to 2 groups: - Group 1: Patients confirmed Wilson's disease. - Group 2: Controls. * Patients group: Patient diagnosed as WD patients, following up in Pediatric Hepatology Clinic in NHTMRI. According to Criteria of diagnosis based on Leipzig scoring system (11,12): Typical clinical symptoms and signs, as: Kayser-Fleischer rings, neurological symptoms, serum ceruloplasmin, Coombs-negative hemolytic anemia. Other tests: Liver biopsy, 24hr urinary Cu, gene analysis.

You may qualify if:

• Confirmed diagnosis of Wilson's disease based on Leipzig scoring criteria (including clinical signs, Kayser-Fleischer rings, low ceruloplasmin, or genetic analysis).
• Age between 4 years and 18 years.
• Written informed consent obtained from parents or legal guardians.

You may not qualify if:

• Children with clinical evidence of overt heart failure or known congenital heart disease.
• Children suffering from fulminant hepatitis.
• Known co-existing primary liver diseases other than Wilson's disease.
• Presence of syndromic disorders or major congenital anomalies.

Sponsors & Collaborators

• Hebatullah Fawzy: lead

Study Sites (2)

Faculty of medicine AinShams U

Cairo, Egypt

Location

National Hepatology and Tropical Research Institute (NHTMRI)

Giza, Egypt

Location

Related Publications (14)

• 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.

  PMID: 28753182 RESULT

• 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.

  PMID: 40089450 RESULT

• 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.

  PMID: 22340672 RESULT

• https://ebm.one/en/chapter-table/scoring-system-developed-8th-international-meeting-wilson-disease-leipzig-2001

  RESULT

• https://doi.org/10.4236/wjcd.2019.93018

  RESULT

• 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.

  PMID: 31947878 RESULT

• 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.

  PMID: 34162411 RESULT

• 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.

  PMID: 34286869 RESULT

• 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.

  PMID: 30691535 RESULT

• https://doi.org/10.21608/cupsj.2021.71046.1018

  RESULT

• 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.

  PMID: 34572285 RESULT

• 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.

  PMID: 38397079 RESULT

• https://doi.org/10.1038/s41598-024-59377-w

  RESULT

• 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.

  PMID: 38660122 RESULT

MeSH Terms

Conditions

Hepatolenticular Degeneration; Ventricular Dysfunction, Left

Interventions

Echocardiography; Electrocardiography

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis

Study Officials

• Hebatullah I Fawzy, Msc Student

  Faculty of medicine AinShams U,National Hepatology and Tropical Research Institute (NHTMRI)

  PRINCIPAL INVESTIGATOR

• Eman M ElSayed (Assistant Professor of Pediatrics), AssProfessor

  Faculty of Medicine AinShams U

  STUDY CHAIR

• Mona AH Khafagy (Lecturer of Pediatrics), Lecturer

  Faculty of Medicine AinShams U

  STUDY DIRECTOR

• Sara M Osman (Teaching Fellow of Pediatrics), PedFellow

  National Hepatology and Tropical Research Institute (NHTMRI)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: (Principal Investigator / Postgraduate Master's Student / ASU / Pediatric Resident /NHTMRI)

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 14, 2026
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 14, 2026

Record last verified: 2026-08

Locations

EG (2)