Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan

Eda, Keisuke; Mizuochi, Tatsuki; Iwama, Itaru; Inui, Ayano; Etani, Yuri; Araki, Mariko; Hara, Shinya; Kumagai, Hideki; Hagiwara, Shin-ichiro; Murayama, Kei; Murakami, Jun; Shimizu, Norikazu; Kodama, Hiroko; Yasuda, Ryosuke; Takaki, Yugo; Yamashita, Yushiro

doi:10.1111/jgh.13812

Cited by 23 publications

(25 citation statements)

References 16 publications

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“…Early diagnosis, particularly in the presymptomatic period, can greatly improve the prognosis of WD patients. Unfortunately, clinical symptoms during very early childhood are usually mild or atypical (Carlson, Al‐Mateen, & Brewer, ; Eda et al, ; Wiernicka et al, ). The majority of patients with WD develop symptoms between 5 and 35 years of age.…”

Section: Introductionmentioning

confidence: 99%

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Lin

et al. 2019

American J of Med Genetics Pt A

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Wilson disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene. Clinical features and mutational analysis of Chinese children with WD at early age were rarely described. Herein, we retrospectively examined 114 children with WD at the mean of 5.9 years old age at diagnosis. Eight patients developed acute liver failure at mean age of 9.7 years old, 4 of whom died. Among the 114 patients, 86.0%were presymptomatic with isolated elevation of transaminases at diagnosis, 99.1% had decreased ceruloplasmin, and 68.4% had urinary copper excretion over 100 μg/24 hr.Bi-allele pathogenic ATP7B mutations were identified in all patients. Among the 60 mutations detected, 10 were novel, including 7 missense mutations (p.I566N, p.

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Section: Introductionmentioning

confidence: 99%

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Lin

et al. 2019

American J of Med Genetics Pt A

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“…Since zinc has extremely low toxicity and is also cost effective, it is an optimal therapeutic choice. It has been successfully used as first-line treatment for treating pre-symptomatic and pregnant patients for maintaining their copper levels consistently, and in pediatric WD patients with hepatic presentation 26,27 .…”

Section: Discussionmentioning

confidence: 99%

“Combined Sodium Dimercaptopropanesulfonate and Zinc versus D-penicillamine as First-line Therapy for Neurological Wilson’s disease”

Zhang

Xiao

Yang

2020

Preprint

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Background: Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson’s diseases (WD), the current treatment options available for WD are still limited, expecially for WD patients with neurological symptoms. Objective: The aim of this study was to compare the course of treatment for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy. Methods: The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients were treated with intravenous DMPS+Zinc and in combination with oral Zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS). The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed. Results: 93 patients in Group 1, displayed decreased GAS scores consistently in comparison to the baseline (P < 0.01). Among them, 82(88.2%) patients displayed a significant improvement in their neurological status after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) displayed neurological improvements, while 17 patients (26.2%) experienced neurological deterioration at 1-year follow up. 6 patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio ( P < 0.01) and lower worsening ratio of the neurological symptoms of the patients ( P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and the blood cell counts remained stabilized in group1. Conclusions: This study suggests that the combined therapeutic approach of treatment with DPMS and zinc should be the preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA, as the experimental data demonstrates that it is significantly more efficient.

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“…A population scale screening program is highly desirable for making early diagnosis. Furthermore, the recent use of oral zinc in the treatment of early diagnosed cases (before 10 years old) is highly promising with little side effect (15). Together with the natural history of WD, we propose to utilities this new screening window targeting preschool children or school children before 10 years-of-age.…”

Section: Discussionmentioning

confidence: 99%

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson’s disease

Tang

Hui

Huang

et al. 2019

Preprint

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43Background: 44 With spot urine collected from a large control sample of preschool children (aged 3-7 years), 45 reference range of spot urine copper excretion indexes and their biological variation were defined. 47Methods: 48In order to investigate their test performance in screening of Wilson disease in this age group, 49 multiple spot urine samples from 6 WD patients diagnosed at presymptomatic stage were analysed. 50 Cut-off values for spot urine copper concentration, copper to creatinine ratio and copper to 51 osmolality ratio at 0.5 µmol/L, 0.1 µmol/mmol and 0.00085 µmol/mOsmol (32 µg/L, 56 µg/g 52 creatinine and 0.054 µg/mOsmol, respectively, in conventional units) have potential application in 53 differentiation of WD patients. 54 55 Results: 56 The data provides a new insight that the inter-individual variation of spot urine copper indexes 57 (CVg) were moderate with figures around 60% which was similar to other clinically useful urine 58 tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with 59both urine creatinine and osmolality. And more than 95% of data points in health preschool children 60 fell within prediction regions by linear regression suggesting a good utility of normalisation by these 61 2 analytes. Receiver operator curve (ROC) showed that copper to osmolality ratio was the best 62 index with an area under curve (AUC) greater than 0.98. 63 64 109 important in the interpretation of all laboratory test results. Although large scale programs like 110 CALIPER have been set up to better define RI in the paediatric age group, they are confined to 111 analytes in serum or blood samples (12). It is reasonable as they are more commonly encountered in 112 routine laboratories.113 114 157 for controls. In addition, the prediction region covering the predicted distribution of 95% control 158 data points were shown (blue rectangles in scatter plots, e.g. figure 2). Difference in spot urine 159 indexes are compared between WD and control by non-parametric group-wise statistics (Wilcoxon 160 test). Statistical significance was defined by type I error of 0.05.161 162

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Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan

Cited by 23 publications

References 16 publications

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

“Combined Sodium Dimercaptopropanesulfonate and Zinc versus D-penicillamine as First-line Therapy for Neurological Wilson’s disease”

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson’s disease

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