Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

Sánchez‐Monteagudo, Ana; Ripollés, Edna; Berenguer, Marina; Espinós, Carmen

doi:10.3390/biomedicines9091100

Cited by 24 publications

(19 citation statements)

References 158 publications

(194 reference statements)

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“…In the work carried out on a 3D culture of hepatocytes, it was also shown that the release of AST into the culture medium is especially high when cells are exposed to preparations, the toxic effect of which is related with mitochondrial dysfunction [ 67 ]. At the same time, our data are consistent with the information that in Wilson–Konovalov’s disease characterized by the accumulation of excess copper amounts in liver cells, a predominant increase in AST activity is recorded in the blood serum, and therefore the AST/ALT ratio exceeding 2 is considered one of the clinical indicators of this pathology [ 73 , 74 ]. In addition, the fact that the appearance of mitochondrial enzymes in blood serum under pathological conditions is usually observed later than cytoplasmic enzymes [ 75 ] may explain a significant AST activity growth in the culture medium at later stages of incubation with CuAc 2 .…”

Section: Resultssupporting

confidence: 91%

“…Substitution of zinc in the catalytic centers of the enzyme also explains the reduction in the ALP activity level of the blood serum observed in patients with Wilson–Konovalov disease, especially when it manifests itself in the fulminant form accompanied by extensive necrosis of the liver [ 77 , 78 ]. In the case of this disease characterized by the accumulation of excessive amounts of copper in the liver, a decrease the ALP activity in serum does not reflect the degree of hepatocellular damage but is one of the diagnostic signs indicating the toxic effect of copper [ 73 , 74 , 79 ]. A similar effect of copper preparations on ALP activity was also previously described; however, in contrast to our results, in these studies, only complexes of myo-inositol hexakisphosphate with Cu (II) ions but not free copper ions had an inactivating effect (the enzyme activity decreased by 99%) [ 80 , 81 ].…”

Section: Resultsmentioning

confidence: 99%

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Evaluation of the Safety and Toxicity of the Original Copper Nanocomposite Based on Poly-N-vinylimidazole

et al. 2021

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A new original copper nanocomposite based on poly-N-vinylimidazole was synthesized and characterized by a complex of modern physicochemical and biological methods. The low cytotoxicity of the copper nanocomposite in relation to the cultured hepatocyte cells was found. The possibility to involve the copper from the nanocomposite in the functioning of the copper-dependent enzyme systems was evaluated during the incubation of the hepatocyte culture with this nanocomposite introduced to the nutrient medium. The synthesized new water-soluble copper-containing nanocomposite is promising for biotechnological and biomedical research as a new non-toxic hydrophilic preparation that is allowed to regulate the work of key enzymes involved in energy metabolism and antioxidant protection as well as potentially serving as an additional source of copper.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Evaluation of the Safety and Toxicity of the Original Copper Nanocomposite Based on Poly-N-vinylimidazole

et al. 2021

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“…A score of 4 and more points confirms WD. Unfortunately, the assessment based on the Leipzig scoring system does not always provide evident conclusions [ 67 , 68 ] and although genetic testing is currently more available, some patients still cannot obtain it. The criteria for WD diagnosis included in the Leipzig score are presented in Table 1 .…”

Section: Diagnostic Approach To Patients With Wilson’s Disease Suspicionmentioning

confidence: 99%

Wilson’s Disease: An Update on the Diagnostic Workup and Management

Kasztelan-Szczerbińska

Cichoż‐Lach

2021

JCM

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Wilson’s disease (WD) is a rare autosomal recessive disorder of hepatocellular copper deposition. The diagnostic approach to patients with WD may be challenging and is based on a complex set of clinical findings that derive from patient history, physical examination, as well as laboratory and imaging testing. No single examination can unequivocally confirm or exclude the disease. Timely identification of signs and symptoms using novel biomarkers and modern diagnostic tools may help to reduce treatment delays and improve patient prognosis. The proper way of approaching WD management includes, firstly, early diagnosis and prompt treatment introduction; secondly, careful and lifelong monitoring of patient compliance and strict adherence to the treatment; and, last but not least, screening for adverse effects and evaluation of treatment efficacy. Liver transplantation is performed in about 5% of WD patients who present with acute liver failure at first disease presentation or with signs of decompensation in the course of liver cirrhosis. Increasing awareness of this rare inherited disease among health professionals, emphasizing their training to consider early signs and symptoms of the illness, and strict monitoring are vital strategies for the patient safety and efficacy of WD therapy.

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“…As it is known, ceruloplasmin levels are reduced in Wilson disease, in which copper cannot be involved into ceruloplasmin in the liver due to defects in the copper-transporting ATPase 2. Serum ceruloplasmin is the major diagnostic criteria for Wilson disease [ 45 , 46 ]. The alteration in the degree of copper and ceruloplasmin oxidase activity in human amniotic fluid from 20 weeks’ gestation to term was detected.…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteomic Assessment of Normal vs. Polyhydramnios Amniotic Fluid Based on Computational Analysis

et al. 2022

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Mass spectrometry-based proteomics have become a valued tool for conducting comprehensive analyses in amniotic fluid samples with pathologies. Our research interest is the finding and characterization of proteins related to normal vs. polyhydramnios (non-immune hydrops) pregnancy. Proteomic analysis was performed on proteins isolated from fresh amniotic fluid samples. Proteins were fractionated by 2DE using a different pI range (pI 3–11, pI 4–7) and analyzed with MALDI-TOF-MS. Furthermore, by using computational analysis, identified proteins in protein maps specific to normal vs. polyhydramnios pregnancy were compared and the quantities of expressed proteins were evaluated mathematically. Comparative analysis of proteome characteristic for the same polyhydramnios pregnancy fractionated by 2DE in different pI range (3–11 and 4–7) was performed and particular protein groups were evaluated for the quantification of changes within the same protein level. Proteins of normal and polyhydramnios pregnancies were fractionated by 2DE in pI range 3–11 and in pI range 4–7. Mass spectrometry analysis of proteins has revealed that the quantity changes of the main identified proteins in normal vs. polyhydramnios pregnancy could be assigned to immune response and inflammation proteins, cellular signaling and regulation proteins, metabolic proteins, etc. Specifically, we have identified and characterized proteins associated with heart function and circulatory system and proteins associated with abnormalities in prenatal medicine. The following are: serotransferrin, prothrombin, haptoglobin, transthyretin, alpha-1-antitrypsin, zinc-alpha-2-glycprotein, haptoglobin kininogen-1, hemopexin, clusterin, lumican, afamin, gelsolin. By using computational analysis, we demonstrated that some of these proteins increased a few times in pathological pregnancy. Computer assistance analysis of 2DE images suggested that, for the better isolation of the proteins’ isoforms, those levels increased/decreased in normal vs. polyhydramnios pregnancy, and the fractionation of proteins in pI rage 3–11 and 4–7 could be substantial. We analyzed and identified by MS proteins specific for normal and polyhydramnios pregnancies. Identified protein levels increased and/or modification changed in case of non-immune hydrops fetus and in cases of cardiovascular, anemia, growth restriction, and metabolic disorders. Computational analysis for proteomic characterization empower to estimate the quantitative changes of proteins specific for normal vs. polyhydramnios pregnancies.

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Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

Cited by 24 publications

References 158 publications

Evaluation of the Safety and Toxicity of the Original Copper Nanocomposite Based on Poly-N-vinylimidazole

Evaluation of the Safety and Toxicity of the Original Copper Nanocomposite Based on Poly-N-vinylimidazole

Wilson’s Disease: An Update on the Diagnostic Workup and Management

Comparative Proteomic Assessment of Normal vs. Polyhydramnios Amniotic Fluid Based on Computational Analysis

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