Adherence to treatment, a challenge even in treatable metabolic rare diseases: A cross sectional study of Wilson's disease

Jacquelet, Elodie; Poujois, Aurélia; Pheulpin, Marie-Christine; Demain, Adèle; Tinant, Nadège; Gastellier, Nathalie

doi:10.1002/jimd.12430

Cited by 29 publications

(24 citation statements)

References 35 publications

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“…Liver disorders frequently worsened in screened patients (43%), in contrast to the other groups. Poor adherence to treatment in these asymptomatic patients may explain this deterioration 45 . In our cohort, 3 screened patients followed only a low‐copper diet and did not worsen after 7 years of follow‐up.…”

Section: Discussionmentioning

confidence: 75%

“…Poor adherence to treatment in these asymptomatic patients may explain this deterioration. 45 In our cohort, 3 screened patients followed only a low-copper diet and did not worsen after 7 years of follow-up. Simple but regular follow-up visits could therefore be discussed in the exceptional cases of asymptomatic patients with normal copper levels, although an expert opinion is crucial in this decision.…”

Section: Discussionmentioning

confidence: 85%

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Diagnosis and Outcomes of Late‐Onset Wilson's Disease: A National Registry‐Based Study

et al. 2022

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Background Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late‐onset forms. Objective The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late‐onset WD. Methods Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow‐up. Results Forty‐five patients were identified (median age: 49, range: 40–64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid‐attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser–Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24‐h urinary copper excretion was normal in 33% of patients at diagnosis. Conclusions In the FWDR, late‐onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long‐lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 85%

Diagnosis and Outcomes of Late‐Onset Wilson's Disease: A National Registry‐Based Study

et al. 2022

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“…One of the above three patients with late neurological deterioration in our study had poor compliance. It has been reported that 25–32% of WD patients have low adherence to the treatment, which is very challenging for the long-term management of WD patients ( Maselbas et al, 2019a ; Maselbas et al, 2019b ; Jacquelet et al, 2021 ). There is no doubt that non-compliance has an important negative impact not only on clinical outcomes of WD patients, but also on education level and work ability, regardless of the disease form ( Maselbas et al, 2019b ).…”

Section: Discussionmentioning

confidence: 99%

“…Maselbas et al has reported that clinical worsening was noted in 52.2% of treatment non-persistent patients with WD ( Maselbas et al, 2019a ). Several factors may help improve treatment adherence of WD patients including family support, higher education, multidisciplinary management on a case-by-case basis, available medicine from community pharmacies, and once-daily dosage ( Maselbas et al, 2019a ; Jacquelet et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Analysis in Neurological Wilson’s Disease Patients With Neurological Worsening Following Chelator Therapy

et al. 2022

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Objectives: None of the previous studies have focused on the genetic effect on neurological worsening in neurological Wilson’s disease (WD) patients following chelator therapy. We aimed to evaluate the clinical and genetic role in the occurrence of neurological worsening.Methods: We retrospectively reviewed the medical records of neurological WD patients who received initial chelator therapy and genetic test. Clinical, laboratory, and genetic data were collected. The genotype was classified into two types: 1) severe mutation genotype: patients who carried at least one of the following three types of mutations: frameshift mutation, splicing mutation, or nonsense mutation; 2) non-severe mutation genotype: patients who only carried missense mutations. Then, the clinical features and genotype of the patients with and without neurological worsening were investigated.Results: Forty-seven neurological WD patients were identified with a median age at onset of 16.17 years (range 7.75–47 years) and 35 (74.5%) males. The mean interval from onset to diagnosis was 0.6 years (range: 0.5 months-6.25 years). Neurological deterioration was observed in 29 patients (61.7%) and the other 18 patients (38.3%) were stable or improved during anti-copper treatment. The neurological worsening was completely irreversible in 6 cases (20.7%) and partially irreversible in 16 cases (55.2%). The common deteriorated symptoms were as follows: rigidity in 20 cases (69%), speech difficulties in 20 cases (69%)), walking difficulties in 13 cases (44.8%), dysphagia in 9 cases (31%), and salivation in 9 cases (31%). The patients with neurological worsening had significantly younger age (p = 0.028), shorter delayed diagnosis time (p = 0.011), higher rate of dystonia (p = 0.003), and severe mutation genotype (p = 0.036), compared to those without neurological worsening.Conclusion: We found that younger age of onset, the presence of dystonia, and genotype with severe mutations may be predictive of neurological worsening in the neurological WD patients that received chelator therapy. For those patients, chelator therapy should be given with caution and needs closer observation during follow-up.

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“…Differing from the action of chelators, zinc—in either sulfate, gluconate, or acetate forms—reduces the intestinal absorption of copper, thereby leading to the normalization of free copper levels, depletion of stored copper, and appreciable clinical improvement [ 37 , 130 , 131 ]. However, treatment compliance is a challenge, as for all WD treatments [ 132 ], and non-compliance results in deterioration [ 133 ]. Although a few studies have failed to identify zinc therapy as being effective in hepatic impairment of WD patients [ 107 ], these studies were retrospective, and no rigorous dose–response or adherence studies are available.…”

Section: Effectiveness and Safety Profile Of Treatment Optionsmentioning

confidence: 99%

The Role of Zinc in the Treatment of Wilson’s Disease

Avan

Członkowska

Gaskin

et al. 2022

IJMS

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Wilson’s disease (WD) is a hereditary disorder of copper metabolism, producing abnormally high levels of non-ceruloplasmin-bound copper, the determinant of the pathogenic process causing brain and hepatic damage and dysfunction. Although the disease is invariably fatal without medication, it is treatable and many of its adverse effects are reversible. Diagnosis is difficult due to the large range and severity of symptoms. A high index of suspicion is required as patients may have only a few of the many possible biomarkers. The genetic prevalence of ATP7B variants indicates higher rates in the population than are currently diagnosed. Treatments have evolved from chelators that reduce stored copper to zinc, which reduces the toxic levels of circulating non-ceruloplasmin-bound copper. Zinc induces intestinal metallothionein, which blocks copper absorption and increases excretion in the stools, resulting in an improvement in symptoms. Two meta-analyses and several large retrospective studies indicate that zinc is equally effective as chelators for the treatment of WD, with the advantages of a very low level of toxicity and only the minor side effect of gastric disturbance. Zinc is recommended as a first-line treatment for neurological presentations and is gaining acceptance for hepatic presentations. It is universally recommended for lifelong maintenance therapy and for presymptomatic WD.

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Adherence to treatment, a challenge even in treatable metabolic rare diseases: A cross sectional study of Wilson's disease

Cited by 29 publications

References 35 publications

Diagnosis and Outcomes of Late‐Onset Wilson's Disease: A National Registry‐Based Study

Diagnosis and Outcomes of Late‐Onset Wilson's Disease: A National Registry‐Based Study

Clinical and Genetic Analysis in Neurological Wilson’s Disease Patients With Neurological Worsening Following Chelator Therapy

The Role of Zinc in the Treatment of Wilson’s Disease

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