Compound load of copper and iron in the livers of pretreatment patients with Wilson's disease

Harashima, Ai; Hattori, Ai; Hayashi, Hisao; Wakusawa, Shinya; Kusakabe, Atsuhiko; Fujita, Yoshikazu; Tanaka, Minoru; Yano, Motoyoshi; Yoshioka, Kentaro

doi:10.1002/jtra.10054

Cited by 7 publications

(11 citation statements)

References 13 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Regardless of the initial symptoms, their livers were affected by copper toxicosis, resulting in either chronic hepatitis or cirrhosis. The compound overload of copper and iron in the patients was reported in detail elsewhere 15–17 . Histochemical tests for cuprothioneins should be positive in this disease, but were negative in one patient because of a sampling error.…”

Section: Introductionmentioning

confidence: 51%

“…Because ceruloplasmin is a major ferroxidase, iron transport is also affected in the liver and other iron storage organs of hypoceruloplasminemic patients. Their hepatocellular lysosomes might thus be shared by cuprothioneins and iron complex 15–17 . 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.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Hayashi

Wakusawa

Yano

et al. 2007

Hepatology Research

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 51%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the iron load in WD was not discussed in the study. In previous studies, we reported the co-existence of copper and iron in hepatocyte lysosomes of WD patients without HH traits [15,17]. It must be emphasized that the methods applied here have at least 2 advantages over the traditional methods [18].…”

Section: S Motonishi Et Al 412mentioning

confidence: 97%

“…In a previous study, we reported the compound load of copper and iron in the livers of pretreatment patients with WD [17]. Almost the same distribution of copper and sulfur in the electron dense bodies suggested that copper formed a sulfhydryl-rich complex, metallothionein.…”

mentioning

confidence: 89%

See 1 more Smart Citation

Copper- and Iron-rich Matrices in Hepatocellular Lipofuscin Particles of a Young Male Patient: Diagnostic Ultrastructures for Wilson Disease

Motonishi

Hayashi

Fujita

et al. 2006

Ultrastructural Pathology

Self Cite

View full text Add to dashboard Cite

A 17-year-old male patient appeared with the biochemical liver damage associated with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a compound heterozygosity of ATP7B responsible for the primary copper toxicosis of Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic nodules of large-sized hepatocytes with fatty change and those of fat-free small-sized hepatocytes. Histochemically, iron was distributed diffusely in the small-sized hepatocytes, while copper grains appeared in a few of the hepatocytes near the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1% osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex formation of copper with sulfur, and iron with phosphorus in the hepatocyte lipofuscin particles, (2) intraparticle localization of the cuprothionein in the less dense matrix and ferric proteins in the dense matrix, and (3) high affinity of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is the major ferroxidase essential for iron efflux, iron deposits in the hypoceruloplasminemic patients with Wilson disease are not a complication, but a natural event. This study disclosed for the first time the diagnostic ultrastructures of Wilson disease, which might represent different detoxification processes to the reactive metals of copper and iron.

show abstract

Compound overload of copper and iron in patients with Wilson's disease

et al. 2006

View full text Add to dashboard Cite

This review of the copper-iron interaction in Wilson's disease was mainly based on ten patients (three females and seven males) studied in our institutes because the genetic tests of ATP7B for Wilson's disease of primary copper toxicosis and HFE for hemochromatosis, the biochemical parameters of copper and iron, and morphological studies on biopsied liver specimens were complete. All patients had hypoceruloplasminemia and hepatic lesions compatible with Wilson's disease. One patient was homozygous and nine patients were compound heterozygous for the mutations in ATP7B, and all patients were free from the major mutation, C282Y, of HFE. The biochemical parameters of iron metabolism were not specific, except for serum ferritin concentration. Judging from the traditional criteria, seven patients had hyperferritinemia. Histochemical iron was stained in the livers of seven patients and histochemical copper was found in nine patients. Microanalysis was more sensitive than histochemistry, detecting copper and iron accumulation in the hepatocellular lipofuscin particles of all patients. Using an improved fixative, intralipofuscin distribution was found to be different between cuprothionein and iron complexes. Iron overload in Wilson's disease might be worsened after treatment because of the close relation to hypoceruloplasminemia, in which the iron efflux from the liver to the circulation is disturbed.

show abstract

Compound load of copper and iron in the livers of pretreatment patients with Wilson's disease

Cited by 7 publications

References 13 publications

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

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

Copper- and Iron-rich Matrices in Hepatocellular Lipofuscin Particles of a Young Male Patient: Diagnostic Ultrastructures for Wilson Disease

Compound overload of copper and iron in patients with Wilson's disease

Contact Info

Product

Resources

About