Iron accumulation in the liver of male patients with Wilson's disease

Shiono, Yuhta; Wakusawa, Shinya; Hayashi, Hisao; Takikawa, Toshikuni; Yano, Motoyoshi; Okada, Toshihide; Mabuchi, Hiroshi; Kono, Satoshi; Miyajima, Hiroaki

doi:10.1111/j.1572-0241.2001.05269.x

Cited by 96 publications

(47 citation statements)

References 37 publications

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“…The compound overload of copper and iron in the patients was reported in detail elsewhere. [15][16][17] Histochemical tests for cuprothioneins should be positive in this disease, but were negative in one patient because of a sampling error. Because ceruloplasmin is a major ferroxidase, hypoceruloplasminemic patients are also affected by iron overload.…”

Section: Patients With Hemochromatosis Wilson Disease and Dubin-johnmentioning

confidence: 90%

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Genetic background of Japanese patients with adult‐onset storage diseases in the liver

Hayashi

Wakusawa

Yano

et al. 2007

Hepatology Research

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In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with hemochromatosis of unknown etiology, Wilson disease of primary copper toxicosis, and the black liver of Dubin-Johnson syndrome. Three patients with middle-age onset hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and iron complex. Six patients with Dubin-Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices.

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Section: Patients With Hemochromatosis Wilson Disease and Dubin-johnmentioning

confidence: 90%

“…Their hepatocellular lysosomes might thus be shared by cuprothioneins and iron complex. [15][16][17] The histochemistry for iron and copper is not so sensitive that X-ray microanalysis is recommended for the liver specimens obtained from patients with Wilson disease (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

Genetic background of Japanese patients with adult‐onset storage diseases in the liver

Hayashi

Wakusawa

Yano

et al. 2007

Hepatology Research

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“…Peripheral Cp is also depleted in Wilson’s disease, which is primarily a disorder of copper homeostasis, caused by a genetic mutation to ATP7b (Bull et al, 1993). Copper accumulates in liver and brain, along with iron (Shiono et al, 2001; Litwin et al, 2013). Why does iron also accumulate as a result of the disease?…”

Section: Iron Accumulation In the Brainmentioning

confidence: 99%

A delicate balance: Iron metabolism and diseases of the brain

Hare¹,

Ayton²,

Bush³

et al. 2013

Front. Aging Neurosci.

354

298

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Iron is the most abundant transition metal within the brain, and is vital for a number of cellular processes including neurotransmitter synthesis, myelination of neurons, and mitochondrial function. Redox cycling between ferrous and ferric iron is utilized in biology for various electron transfer reactions essential to life, yet this same chemistry mediates deleterious reactions with oxygen that induce oxidative stress. Consequently, there is a precise and tightly controlled mechanism to regulate iron in the brain. When iron is dysregulated, both conditions of iron overload and iron deficiencies are harmful to the brain. This review focuses on how iron metabolism is maintained in the brain, and how an alteration to iron and iron metabolism adversely affects neurological function.

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“…Aceruloplasminemia first found in a Japanese patient is a severe type of iron overload syndrome, 14 and subsequent studies confirmed that hypoceruloplasminemic male patients with Wilson disease were also affected by hepatic iron overload. 6 Subcellular iron first stimulates synthesis of apoferritin containing phosphorus atoms in its core. Thus, ferritin grains polymerized in lysosomes, namely hemosiderin, simultaneously yield specific X-rays of iron and phosphorus.…”

Section: Mpaired Secretion Of Copper Into Bile Is Causedmentioning

confidence: 99%

“…For example, copper overload might be associated with iron overload in hypoceruloplasminemic patients, or replaced by iron overload after long-term chelation therapy due to further reduced levels of ceruloplasminemia. 6 Without special stain or microanalysis of biopsy liver specimens, misdiagnosis or late diagnosis may occur in some patients. When liver specimens were processed with a standard fixative solution of a 2.0% osmium tetroxide, most cupprothioneins were lost during the subsequent processes of embedding, sectioning, and staining for X-ray probe microanalysis.…”

Section: Introductionmentioning

confidence: 99%