Biochemical testing for the diagnosis of Wilson's disease: A systematic review

Salman, Hafiz Muhammad; Amin, Mahwish; Syed, Javaria; Sarfraz, Zouina; Sarfraz, Azza; Sarfraz, Muzna; Bajaña, María José Farfán; Félix, Miguel; Chérrez-Ojeda, Iván

doi:10.1002/jcla.24191

Cited by 9 publications

(14 citation statements)

References 22 publications

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“…For this reason, even analyses with the most advanced technologies, including next-generation sequencing, require additional tests, including biochemical evidence of abnormal copper metabolism, to confirm the diagnosis of WND [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Wilson’s Disease—Genetic Puzzles with Diagnostic Implications

2023

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(1) Introduction: Wilson’s disease (WND) is an autosomal recessive disorder of copper metabolism. The WND gene is ATP7B, located on chromosome 13. WND is characterized by high clinical variability, which causes diagnostic difficulties. (2) Methods: The PubMed, Science Direct, and Wiley Online Library medical databases were reviewed using the following phrases: “Wilson’s disease”, “ATP7B genotype”, “genotype-phenotype”, “epigenetics”, “genetic modifiers”, and their combinations. Publications presenting the results of experimental and clinical studies, as well as review papers, were selected, which concerned: (i) the diversity of genetic strategies and tests used in WND diagnosis; (ii) the difficulties of genetic diagnosis, including uncertainty as to the pathogenicity of variants; (iii) genetic counseling; (iv) phenotypic effects of ATP7B variants in patients with WND and in heterozygous carriers (HzcWND); (v) genetic and epigenetics factors modifying the clinical picture of the disease. (3) Results and conclusions: The genetic diagnosis of WND is carried out using a variety of strategies and tests. Due to the large number of known variants in the ATP7B gene (>900), the usefulness of genetic tests in routine diagnostics is still relatively small and even analyses performed using the most advanced technologies, including next-generation sequencing, require additional tests, including biochemical evidence of abnormal copper metabolism, to confirm the diagnosis of WND. Pseudodominant inheritance, the presence of three various pathogenic variants in the same patient, genotypes indicating the possibility of segmental uniparental disomy, have been reported. Genotype–phenotype relationships in WND are complex. The ATP7B genotype, to some extent, determines the clinical picture of the disease, but other genetic and epigenetic modifiers are also relevant.

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Section: Resultsmentioning

confidence: 99%

Wilson’s Disease—Genetic Puzzles with Diagnostic Implications

2023

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“…It first develops superiorly, then inferiorly, and, finally, in the lateral and medial areas of the cornea. These occur in approximately 40% of patients with hepatic manifestations and in about 95% of patients with neurologic manifestations [ 8 , 17 , 18 ].…”

Section: Wilson’s Disease (Hepatolenticular Degeneration Omim #27790)mentioning

confidence: 99%

“…Both the clinical picture and laboratory test results are not specific to Wilson’s disease. The most important tests in the diagnostics of Wilson’s disease involve the concentration levels of ceruloplasmin in the blood plasma, 24 h urinary copper excretion, and molecular tests [ 10 , 15 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Wilson’s Disease (Hepatolenticular Degeneration Omim #27790)mentioning

confidence: 99%

Disorders of Copper Metabolism in Children—A Problem too Rarely Recognized

Więcek,

Paprocka

2024

Metabolites

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Copper plays an important role in metabolic processes. Both deficiency and excess of this element have a negative effect and lead to pathological conditions. Copper is a cofactor of many enzymatic reactions. Its concentration depends on the delivery in the diet, the absorption in enterocytes, transport with the participation of ATP7A/ATP7B protein, and proper excretion. Copper homeostasis disorders lead to serious medical conditions such as Menkes disease (MD) and Wilson’s disease (WD). A mutation in the ATP7A gene is the cause of Menkes disease, it prevents the supply of copper ions to enzymes dependent on them, such as dopamine β-hydroxylase and lysyl oxidase. This leads to progressive changes in the central nervous system and disorders of the connective tissue. In turn, Wilson’s disease is an inherited autosomal recessive disease. It is caused by a mutation of the ATP7B gene encoding the ATP7B protein which means excess copper cannot be removed from the body, leading to the pathological accumulation of this element in the liver and brain. The clinical picture is dominated by the liver, neurological, and/or psychiatric symptoms. Early inclusion of zinc preparations and chelating drugs significantly improves the prognosis in this group of patients. The aim of the study is to analyse, based on the latest literature, the following factors: the etiopathogenesis, clinical picture, diagnostic tests, treatment, prognosis, and complications of disease entities associated with copper disturbances: Menkes disease and Wilson’s disease. In addition, it is necessary for general practitioners, neurologists, and gastroenterologists to pay attention to these disease entities because they are recognized too late and too rarely, especially in the paediatric population.

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“…Обследовано 53 пациента с болезнью Вильсона-Коновалова, в возрасте от 6 до 18 лет Ме 14,1 (11,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)6). Все дети находились на стационарном лечении в гастроэнтерологическом отделении с гепатологической группой ФГАУ «НМИЦ здоровья детей» Минздрава России.…”

Section: материалы и методыunclassified

“…Для болезни Вильсона-Коновалова характерны: лейкопения, нормохромная анемия, тромбоцитопения, снижение церулоплазмина и общей меди, гипоальбуминемия, увеличение уровней аминотрасфераз (в 1,5-50 раз), билирубина, щелочной фосфатазы, гаммаглютамилтранспептидазы [3,13]. Особое внимание отводится определению меди в моче: гиперкупренилурия у пациентов с болезнью Вильсона-Коновалова может достигать более 1500 мкг/сут (норма < 50 мкг/сут) [9,13]. Токсическое действие меди на ткань печени может проявляться в форме жировой дистрофии гепатоцитов, гепатита, фиброза и цирроза печени [7,14].…”

Section: Introductionunclassified

Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis

Kurbatova

Купцова

Bezrukavnikova

et al. 2022

Russian Journal of Immunology

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The pathology in WilsonConovalov disease (WCD) results from impaired excretion of copper, thus leading to its excessive accumulation in tissues. Hypercupreniluria is characteristic to the WCD. Toxic effects of copper on liver tissue can manifest as fatty degeneration of hepatocytes, hepatitis, fibrosis and cirrhosis. Purpose of the present work was as follows: estimation of immune status in children with WD depending on the stage of liver fibrosis. Fifty-three patients with WCD aged 6 to 18 years, were examined. The stage of liver fibrosis was assessed by transient liver elastography using FibroScan F502 (EchoSence, France). The immune status of peripheral blood lymphocytes was examined using CYTOMICS FC500 flow cytofluorimeter (Beckman Coulter, USA). The relative numbers of B lymphocytes (B1 and B2 populations), NK cells, T helper cells, cytotoxic T lymphocytes, Th17 lymphocytes, regulatory T cells, activated T helper cells were assessed in the lymphoid area. All indices of the patients immune status were recalculated for percentage of deviation from the age-dependent reference values. Mass concentration of copper in daily urine was determined by atomic absorption method using AAnalyst 800 spectrometer. Statistical processing was performed by Statistica10.0 program. The WCD patients are characterized by an increase of Т helpers, regulatory Т cells, Th17 lymphocytes and activated Т helpers, along with decrease of cytotoxic Т lymphocytes and NK cells against normal levels. The number of B cells did not depend on the stage of liver fibrosis and was at the lower limit of normal range, or decreased. Upon increase of the liver fibrosis stage, the number of B1 lymphocytes increases and B2 lymphocytes become decreased. The urinary copper content in the examined patients varied from 19 to 835 g/day, being higher than the reference values in 88% of children, with median value of 175 g/day (71-330). A correlation between urinary copper concentration and degree of immune status deviation was revealed (R = 0.63): urinary copper concentration was increased when the number of Th17 lymphocytes, B1 lymphocytes and regulatory T cells became higher, and when the number of B2 lymphocytes decreased. A significant decrease in the population of cytotoxic T lymphocytes (p = 0.034) was observed in children with WCD in the presence of KaiserFleischer ring. Indexes of cellular immunity in children with WCD are an informative tool to assess the severity of liver damage.

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Biochemical testing for the diagnosis of Wilson's disease: A systematic review

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 22 publications

Wilson’s Disease—Genetic Puzzles with Diagnostic Implications

Wilson’s Disease—Genetic Puzzles with Diagnostic Implications

Disorders of Copper Metabolism in Children—A Problem too Rarely Recognized

Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis

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