Insights into the management of Wilson’s disease

Kathawala, Mohmadshakil; Hirschfield, Gideon M.

doi:10.1177/1756283x17731520

Cited by 47 publications

(49 citation statements)

References 99 publications

(199 reference statements)

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“…In addition, blood copper concentration decreased and urine copper concentration increased after administration of penicillamine. These findings were consistent with those observed in human patients with WD . Thus, these findings suggest that penicillamine can be effective in the treatment of cats with PCH, and blood and urine copper concentrations can be used as the markers of the response to treatment.…”

Section: Discussionsupporting

confidence: 89%

Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene

Asada

Kojima

Nagahara

et al. 2018

Veterinary Internal Medicne

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A 9‐month‐old intact crossbred female cat was presented with jaundice, intermittent anorexia and lethargy, increased hepatic enzyme activities, and hyperammonemia. Abdominal ultrasound and computed tomographic examinations determined that the liver had a rounded and irregular margin, and histopathological examination identified excessive accumulation of copper hepatocytes in the liver. Concentrations of both blood and urine copper were higher than in healthy cats. The patient responded well to treatment with penicillamine. Clinicopathological abnormalities and clinical signs improved within 2 months, and the patient was alive for >9 months after starting treatment. Genetic examination determined that the patient and its littermate had a single‐nucleotide variation (SNV, p. T1297R) that impaired the function of the ATP7B gene product; the gene that is mutated in patients with Wilson's disease (WD). Hepatic copper accumulation was believed to be associated with the SNV of the ATP7B gene, and the patient had a genetic disorder of copper metabolism equivalent to WD in humans.

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Section: Discussionsupporting

confidence: 89%

Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene

Asada

Kojima

Nagahara

et al. 2018

Veterinary Internal Medicne

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“…Up to 30% of WD patients have manifested with psychiatric symptoms at the time of diagnosis . WD is mainly diagnosed between ages 5 and 35 years, but it can occur at any age . WD is a common disease, but it is infrequently recognized …”

mentioning

confidence: 99%

Regional morphometric abnormalities and clinical relevance in Wilson's disease

et al. 2019

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Background Morphology builds Wilson's disease's clincal basis. Objectives To detect and quantify regional morphometric abnormalities, in terms of both volume and shape, in patients with Wilson's disease. Methods Twenty‐seven Wilson's disease patients and 24 healthy controls were enrolled. Specific brain structures, including the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, hippocampus, red nucleus, and substantia nigra (SN), were automatically extracted from each participant's T1‐weighted image. Volume abnormalities and correlations with the modified Young scale were investigated. Furthermore, vertex‐based shape analysis was performed to explore region‐specific morphometric abnormalities. Results Significant global volume atrophy and local shape abnormalities were detected and quantified in the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, red nucleus, and SN. Morphometric abnormalities of the caudate, putamen, and thalamus were strong, whereas those of the globus pallidus, amygdala, red nucleus, and SN were weaker. No hippocampal abnormalities were observed. The modified Young scale was found to correlate significantly with the volumes of the bilateral putamen and the right globus pallidus. Shape analysis revealed subregion‐specific atrophy of the bilateral caudate and putamen. They were concentrated in the subregions that project to the limbic and executive cortices. Significant region‐specific atrophy was also detected in the bilateral thalamic subregions that project to the primary motor, sensory, and premotor cortices. Conclusions We found significant morphometric abnormalities of specific structures of interest in patients with Wilson's disease, both globally and locally. These morphometric abnormalities may serve as useful imaging biomarkers for Wilson's disease. © 2019 International Parkinson and Movement Disorder Society

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“…PCA is a non-specific metal chelating agent that is commonly used to treat WD by gradually increasing the prescribed dose from a relatively low baseline dose to a therapeutically effective dose (Joyce, 1990). While the modality of PCA treatment may aggravate neurological symptoms, continued treatment or changes in the prescribed dose may improve the condition (Kathawala and Hirschfield, 2017). For example, Walshe (Walshe and Yealland, 1993) found that PCA was effective in 97 out of 137 patients with WD who presented with neurological symptoms; however, 24 patients had a poor response to PCA treatment, and 20 patients died.…”

Section: Discussionmentioning

confidence: 99%

Application of 9.4T MRI in Wilson Disease Model TX Mice With Quantitative Susceptibility Mapping to Assess Copper Distribution

Han

Dong

et al. 2020

Front. Behav. Neurosci.

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In the current study, we used 9.4-tesla magnetic resonance imaging (9.4T MRI) and inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of copper in the brain samples of a murine model of Wilson's disease (WD) following penicillamine (PCA) treatment. We also evaluated if the distribution of copper in the brain samples of mice was correlated with behavioral symptoms. Results from the behavioral experiments showed that 7 days of PCA treatment decreased the total distance traveled in the open field and the number of rearing and climbing instances among the toxic milk (TX) mice as compared with model group. We also observed that the open arm ratio in the elevated plus-maze (EPM) was reduced, escape latency in the Barnes maze test was increased, and avoidance in the open field was enhanced in TX mice following 14 days of PCA treatment as compared with those in untreated TX mice. We found that PCA treatment for 21-28 days improved the cognitive abilities, exploratory behavior, and movement behavior of TX mice. The PCA-treated mice also exhibited varying degrees of magnetic susceptibilities in the cortex, corpus striatum, hippocampus, and amygdaloid nucleus across the treatment period. Low copper concentrations were found in all of the analyzed brain regions of PCA-treated mice after 21-28 days as compared with the model group (P < 0.05). However, copper concentrations were increased in the primary motor cortex and cerebellum at 7 days post-PCA treatment as compared with those in the model group (P < 0.05). After 14 days of PCA treatment, the copper concentrations in the sensorimotor cortex, corpus striatum, hippocampus, and amygdaloid nucleus were higher than those detected without treatment. The results from a Pearson's correlation analysis revealed that there was a significant (P < 0.05) correlation between copper concentrations and magnetic susceptibility in all of the brain regions that were analyzed. Therefore, our results indicate that copper concentration and magnetic susceptibility are associated with alterations in mood-related behavior, recognition memory, and movement behaviors in TX mice that are treated with PCA. The redistribution of copper in the TX mouse brain during PCA treatment may aggravate changes in behavioral performance.

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Insights into the management of Wilson’s disease

Cited by 47 publications

References 99 publications

Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene

Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene

Regional morphometric abnormalities and clinical relevance in Wilson's disease

Application of 9.4T MRI in Wilson Disease Model TX Mice With Quantitative Susceptibility Mapping to Assess Copper Distribution

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