Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism

Shimizu, Norikazu; Fujiwara, Junko; Ohnishi, S. Tsuyoshi; Sato, Mari; Kodama, Hiroko; Kohsaka, Takao; Inui, Ayano; Fujisawa, Tomoo; Tamai, Hiroshi; Ida, Shinobu; Itoh, Susumu; M, Ito; Horiike, Norio; Harada, Masaru; Yoshino, Makoto; Aoki, Tsugutoshi

doi:10.1016/j.trsl.2010.08.007

Cited by 40 publications

(29 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further advantages of zinc include its lack of serious side effects and safety for long-term use, and the fact that it does not appear to cause worsening of the neurological manifestations of WD (7). In the present patient, the 24-hour urinary copper (normal, 14-63 μg/day) was decreased from 516.2 μg/day to 53.6 μg/day after zinc treatment, which is consistent with the results of a therapeutic study of zinc acetate in Japanese patients with WD (8). The 24-hour urinary excretion of copper reflects the amount of nonceruloplasmin-bound copper in the circulation.…”

Section: Discussionsupporting

confidence: 89%

Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

et al. 2012

Self Cite

View full text Add to dashboard Cite

A 38-year-old woman with Wilson's disease developed neurological deterioration after 25 years of lowdose penicillamine administration. She showed an akinetic-rigid syndrome and cerebellar motor ataxia. Brain MRI showed increased signal intensity at the bilateral pons, midbrain, putamen, and thalamus. 123I-IMP-SPECT revealed a diffuse reduction of cerebral blood flow at the bilateral cerebral hemisphere including the basal ganglia. After the patient's regimen was changed to zinc therapy, her neurological condition gradually improved, and she showed almost complete recovery within two years. Serial MRI and SPECT studies showed a marked improvement in the lesions.

show abstract

Section: Discussionsupporting

confidence: 89%

Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the administration of zinc has some side effects, none of them is so severe. Thus, Zn acetate is a recommended therapy, for longterm management of patients with Wilson's disease (Huster 2010;Shimizu et al 2010).…”

Section: Zinc and Wilson's Diseasementioning

confidence: 99%

Zinc and human health: an update

et al. 2011

View full text Add to dashboard Cite

The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases.

show abstract

“…Zinc is also thought to protect against copper toxicity in the liver by promoting sequestration of free copper in a non-toxic, metallothionein-bound form [105]. Treatment adequacy is determined by measuring non-ceruloplasmin-bound copper levels in the serum (5-15 µg/dL), 24-hour urinary copper excretion (<75 µg/day) [89], or by spot urinary copper excretion with less than 0.075 µg/mg creatinine [106]. Non-ceruloplasmin-bound copper levels in the serum can usually be calculated from serum copper and ceruloplasmin levels using the following equation:…”

Section: Wilson’s Disease (Wd)mentioning

confidence: 99%

Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

Kodama

Fujisawa²,

Bhadhprasit³

2012

CDM

Self Cite

158

151

View full text Add to dashboard Cite

Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome.Wilson’s disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson’s disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson’s disease should be implemented in infants. Patients with Wilson’s disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson’s disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention.

show abstract

Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism

Cited by 40 publications

References 10 publications

Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

Zinc and human health: an update

Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

Contact Info

Product

Resources

About