Category: Rare Genetic and Metabolic Diseases
Objective: To determine the frequency of side effects of long-term copper chelation therapy in Wilson’s disease (WD).
Background: WD is a neurometabolic autosomal recessive disorder caused by ATP7B mutation, resulting in abnormal copper accumulation. Lifelong chelation therapeutics is instituted post-diagnosis with careful monitoring.
Method: We conducted an observational retrospective study of consecutive 96 Wilson’s Disease patients (Leipzig score ≥ 4) from a tertiary referral hospital. Data on demographic characteristics, clinical features and therapy were collected from Neurology and Hepatic outpatient clinical records.
Results: Among 85 eligible patients, 43 (50.6%) were women with a mean age at WD diagnosis of 21.5 ± 12.70 years. The mean follow-up time was 17.7 ± 12,1 years, with 25% of patients being followed more than 25 years. Overall, 82 patients were treated with Penicillamine, 45 with Trientine and 24 with Zinc. Sixty-five (76.5%) developed adverse events under chelator therapy, leading to its suspension in 37 (56.9%) patients.
Early neurological worsening was observed in 14 out of 85 WD patients (16.5%); with 10 (12.2%) under Penicillamine and 4 (8.9%) under Trientine. Neurological worsening was moderate to severe in 85.7% (n=12) of cases, with partial reversibility in 42.9% (n=6) and irreversibility in 28.6% (n=4).
Immunological adverse events were observed in 13 out 85 WD patients (15.3%), including hypersensitivity reactions, glomerulonephritis, autoimmune hepatitis, lupus, and rheumatoid arthritis-like syndromes.
Cytopenia (14.6%), including sideroblastic anemia, proteinuria (7.3%), gastrointestinal intolerance (6.1%) and acquired cutis laxis (1.2%) were also associated with Penicillamine chelation therapy. Gastric intolerance (41.7%) was the most frequent adverse event with Zinc.
Conclusion: Lifelong chelation therapy presents clinical challenges. Penicillamine, in particularly, is associated with several adverse events of varying severity, limiting its long-term use. Neurological worsening succeeding chelation therapy, mostly not reversible, was present in about 17% of the patients.
To cite this abstract in AMA style:
C. Guedes Vaz, H. Pessegueiro, J. Castro Ferreira, J. Gandara, V. Dionísio Lopes, E. Silva, S. Ferreira, C. Pereira, D. Valadares, L. Maia, J. Presa, A. Pinto, A. Costa, C. Rolanda, C. Agostinho, I. Gonçalves, P. Peixoto, R. Costa, S. Lopes, M. Magalhães. Therapeutic challenges of long-standing chelator therapy in Wilson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/therapeutic-challenges-of-long-standing-chelator-therapy-in-wilsons-disease/. Accessed June 14, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/therapeutic-challenges-of-long-standing-chelator-therapy-in-wilsons-disease/