Materiały źródłowe

• #1 Wilson’s disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/wilsons-disease/diagnosis-treatment/drc-20353256

  Liver biopsy is a procedure to remove a small sample of liver tissue for laboratory testing. A liver biopsy is commonly performed by inserting a thin needle through the skin and into the liver. […] Diagnosing Wilson’s disease can be hard because its symptoms often are like other liver diseases, such as hepatitis. Also, symptoms can occur over time. Changes in behavior that come on gradually can be especially hard to link to Wilson’s disease. […] Doctors rely on symptoms and test results to make the diagnosis. Tests and procedures used to diagnose Wilson’s disease include: […] Blood tests can monitor your liver function and check the level of a protein called ceruloplasmin that binds copper in the blood. They can check the level of copper in your blood too. Your doctor also might want to measure the amount of copper removed in your urine during a 24-hour period.

• #1 Wilson’s disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/wilsons-disease/diagnosis-treatment/drc-20353256

  Using a microscope with a high-intensity light, an eye doctor checks your eyes for Kayser-Fleischer rings. This is called a slit-lamp exam. These rings are caused by extra copper in the eyes. Wilson’s disease also is related to a type of cataract, called a sunflower cataract. This cataract can be seen during an eye exam. […] In a biopsy, your doctor inserts a thin needle through your skin and into your liver. Then your doctor draws a small sample of tissue. A laboratory tests the tissue for extra copper. […] A blood test can pinpoint the genetic changes that cause Wilson’s disease. If you have the changed gene that causes Wilson’s disease, doctors also can screen any siblings. If any have the changed gene, that sibling can start treatment before symptoms begin.

• #2 Diagnosis – Wilson Disease Association

  https://wilsondisease.org/do-i-have-wilson-disease/diagnosis/

  How is Wilson disease diagnosed? […] Diagnosis of Wilson disease is often not straightforward. Many tests are usually necessary, and sometimes some of the test results may be inconclusive. No one test is sufficient for a diagnosis, and test results must be considered along with with any symptoms or pre-existing conditions that are also present. […] Diagnosing Wilson disease is challenging for even the most experienced doctors since it can masquerade as many other disorders and is often misdiagnosed, sometimes for many years. Early diagnosis and proper treatment is essential to prevent progression of the disease. […] The diagnosis of Wilson disease is made by relatively simple tests. The tests can diagnose the disease in both symptomatic patients and people who show no signs of the disease.

• #3 Wilson’s disease – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/427

  Wilson’s disease is a systemic disease that can often mimic other conditions, commonly leading to delayed diagnosis or misdiagnosis. It should be considered in patients with abnormal liver enzymes, liver disease, neurological conditions, or psychiatric disorders. […] Investigate all patients with liver function tests, slit-lamp examination for Kayser-Fleischer rings, serum ceruloplasmin, and 24-hour urinary copper measurement. Further investigations (e.g., genetic testing for ATP7B mutations, liver biopsy) may be indicated. No test is capable of diagnosing Wilson’s disease in isolation. The Leipzig score compiles clinical features and investigation results; a score 4 is diagnostic. […] Key diagnostic factors include elevated serum aminotransferases, history of hepatitis, acute liver failure, behavioural abnormalities, presence of Kayser-Fleischer rings, tremor, dysarthria, dystonia, incoordination, and sloppy or small handwriting.

• #4 THINK WILSON

  https://think-wilson.com/diagnosis/

  Diagnosis of Wilson disease is often delayed or it is mistaken for other disorders, which can result in serious consequences for patients, including avoidable disease progression and death. […] A study of 163 patients with Wilson disease revealed a mean delay of ~25 months from symptom onset to diagnosis. […] A roughly three-fold greater delay in patients with neurologic presentation versus hepatic presentation. […] If you see a patient presenting with liver abnormalities, unexplained neurologic movement disorders, or unexplained liver disease in combination with neurologic or neuropsychiatric disorders, a potential diagnosis of Wilson should be considered. […] Wilson disease should also be suspected in patients presenting with non-alcoholic fatty liver disease or pathologic findings of non-alcoholic steatohepatitis.

• #5 Diagnosis – Wilson Disease Association

  https://wilsondisease.org/do-i-have-wilson-disease/diagnosis/

  It is important to diagnose Wilson disease as early as possible, since severe liver damage can occur before there are any signs of the disease. Individuals with Wilson disease may falsely appear to be in excellent health. […] We strongly suggest making an appointment at one of our Centers of Excellence for a diagnosis if possible.

• #6 Wilson disease – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/wilson-disease/

  Wilson disease is an autosomal recessive metabolic disorder in which impaired copper excretion causes copper to accumulate in the body. […] The disease often goes undiagnosed until clinical suspicion is raised by the characteristic combination of hepatitis or cirrhosis, dementia, and parkinsonism. […] Diagnostics involve slit lamp examination and laboratory studies to assess copper metabolism (e.g., ceruloplasmin, urinary copper excretion). […] Genetic testing or liver biopsies with quantitative copper assays may be necessary if the diagnosis is indeterminate. […] Consider a diagnosis of Wilson disease in individuals with: Acute liver failure (ALF) with nonimmune hemolytic anemia (i.e., negative Coombs test), recurrent self-limited hemolysis, unexplained liver disease, especially if accompanied by neuropsychiatric symptoms, a first-degree relative with Wilson disease.

• #7 Wilson disease: Clinical manifestations, diagnosis, and natural history – UpToDate

  https://www.uptodate.com/contents/wilson-disease-clinical-manifestations-diagnosis-and-natural-history

  Wilson disease may be suspected in patients with any of the following: Unexplained liver biochemical abnormalities (eg, elevated aminotransferases), especially if they are accompanied by neurologic or psychiatric symptoms. […] For symptomatic patients, we use a stepwise approach to establish the diagnosis of Wilson disease. Testing begins with an ocular examination for Kayser-Fleischer (KF) rings and laboratory studies. If initial testing is inconclusive, we obtain liver biopsy and/or genetic testing. […] For symptomatic patients with KF rings, the diagnosis of Wilson disease is established if either of following criteria are met: 24-hour urinary copper excretion >40 mcg/24 hours (0.64 micromol/24 hours) in addition to ceruloplasmin <20 mg/dL (200 mg/L), or 24-hour urinary copper excretion >100 mcg/24 hours (1.6 micromol/24 hours), regardless of ceruloplasmin level.

• #7 Wilson disease: Clinical manifestations, diagnosis, and natural history – UpToDate

  https://www.uptodate.com/contents/wilson-disease-clinical-manifestations-diagnosis-and-natural-history

  For patients with inconclusive initial testing who undergo a liver biopsy, we determine hepatic copper concentration: A diagnosis of Wilson disease is established if the hepatic copper concentration is >250 mcg/g dry weight (4 micromol/g dry weight). […] A scoring system for assessing the certainty of the diagnosis was developed at an international meeting in Leipzig, Germany. The scoring system includes biochemical testing (eg, ceruloplasmin, urinary copper excretion), clinical manifestations (KF rings and neurologic symptoms), and molecular testing for ATP7B mutations.

• #8 THINK WILSON

  https://think-wilson.com/diagnosis/

  Wilson disease can manifest at any age and diagnosis of Wilson disease should not be ruled out based on age alone. […] Diagnostic recommendations and algorithms for Wilson disease are available from AASLD, EASL, and ESPGHAN, providing approaches to diagnosis for adult and pediatric patients presenting with a variety of symptoms. […] A single diagnostic test may not provide definitive confirmation so multiple laboratory tests may be required to confirm a diagnosis of Wilson disease. […] Physical examination is an important aspect of diagnosis and it can detect a variety of manifestations, including hepatomegaly, portal hypertension, and chronic liver disease. […] Ophthalmologic examination is another common tool used in the diagnosis of Wilson disease. […] Current diagnostic guidelines also recommend the use of brain imaging, including MRI, as over 90% of patients with Wilson disease with neurologic symptoms have brain pathologies detectable by MRI.

• #8 THINK WILSON

  https://think-wilson.com/diagnosis/

  Many patients with Wilson disease experience diagnostic delay, with a delay of 44.4 months seen in patients with neurologic manifestations versus 14.4 months in those with hepatic manifestations. […] Diagnostic assessments in Wilson disease include laboratory tests for altered copper metabolism and physical and ophthalmologic examinations. […] Wilson disease manifestations may be mild or subtle, requiring thorough diagnostic evaluation, and the disorder should not be ruled out based on age alone or the absence of Kayser-Fleischer rings. […] THE LEIPZIG SCORING SYSTEM (ALSO KNOWN AS THE FERENCI SCORING SYSTEM) MAY HELP TO SIMPLIFY DIAGNOSIS OF WILSON DISEASE BY USING A COMBINATION OF CLINICAL SYMPTOMS AND LABORATORY TESTS WHEN GENETIC TESTING IS NOT FEASIBLE OR GENETIC RESULTS ARE INCONCLUSIVE.

• #9 Wilson Disease: Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/5957-wilson-disease

  To diagnose Wilson disease, your healthcare provider will ask about your family history and personal medical history to identify whether symptoms could be the result of this condition. […] Providers will examine you for other signs that tell them you have problems with your liver, brain or eyes. During an eye exam, your provider will perform a slit-lamp exam, which is a special light that looks for Kayser-Fleischer rings in your eyes. […] If they suspect Wilson disease, your healthcare provider will want to do blood and urine tests. […] The diagnosis of Wilson disease is made using blood tests, urine tests, genetic testing or liver biopsy. […] Blood tests can look at many substances in your blood including: Ceruloplasmin: Ceruloplasmin is a protein that carries copper in the bloodstream. People with Wilson disease often have low ceruloplasmin levels.

• #9 Wilson Disease: Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/5957-wilson-disease

  Your healthcare provider may order a blood test to check for the genetic mutation that causes Wilson disease if other medical tests dont confirm or rule out a diagnosis of the condition. […] For 24 hours, you will collect your urine at home in a special container thats copper-free, provided by your healthcare provider. A lab will check the amount of copper in your urine. Copper levels in the urine are higher than normal in people who have Wilson disease. […] If the results of blood and urine tests dont confirm or rule out a diagnosis of Wilson disease, your provider may order a liver biopsy. During a liver biopsy, your healthcare provider will take a small sample of tissue from your liver. A pathologist will examine the tissue under a microscope to look for features of specific liver diseases, such as Wilson disease, and check for liver damage and cirrhosis. […] If you have nervous system symptoms, your healthcare provider may use imaging tests to check for signs of Wilson disease or other conditions in the brain. Tests could include: MRI, X-ray, CT scan.

• #10 Wilson Disease: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/183456-overview

  Serum ceruloplasmin levels are less than 20 mg/dL (reference range, 20-40 mg/dL) in approximately 90% of all patients with Wilson disease. […] The urinary copper excretion rate is greater than 100 mcg/day (reference range, 40 mcg/day) in most patients with symptomatic Wilson disease, but it may also be elevated in other cholestatic liver diseases. […] In a patient with Kayser-Fleischer rings, a serum ceruloplasmin level 20 mg/dL and 24-hour urine copper excretion 40 mcg/day establish the diagnosis of Wilson disease. […] Hepatic copper concentration (criterion standard) on a liver biopsy specimen is 250 mcg/g of dry weight even in asymptomatic patients; a normal result (15-55 mcg/g) effectively excludes the diagnosis of untreated Wilson disease, but elevation may be found in other chronic hepatic disorders.

• #11 Wilson Disease | Choose the Right Test

  https://arupconsult.com/content/wilson-disease

  Low serum ceruloplasmin levels are suggestive of WD in most patients, especially those with neurologic symptoms, but are less commonly observed in patients with hepatic symptoms. […] The measurement of total copper excreted in urine over a 24-hour period reflects the amount of nonceruloplasmin-bound copper in circulation. The urine copper test can be a useful diagnostic test in many cases, although results are not applicable in the case of renal failure. […] Free serum copper (which does not include ceruloplasmin-bound copper) is generally elevated in patients with untreated WD and is considered to be a better indication of WD than total serum copper. […] High hepatic parenchymal copper concentration is very suggestive of WD, although it may also be observed in other chronic liver disorders or cholestatic conditions.

• #11 Wilson Disease | Choose the Right Test

  https://arupconsult.com/content/wilson-disease

  Generally, genetic testing is performed after biochemical testing to confirm a diagnosis of WD. However, nucleic acid-based testing is gaining popularity as a primary diagnostic tool as variants are identified and the technology advances. Diagnosis of WD relies on detection and identification of biallelic pathogenic variants in ATP7B. […] AASLD and EASL recommend that all first-degree relatives of a patient with confirmed WD be screened for WD. The preferred screening method is mutational analysis, if available. Biochemical screening should include serum copper, ceruloplasmin, and basal 24-hour urinary copper testing; screening should also include a brief patient history for information related to liver disease and subtle features that would suggest neurologic involvement, along with physical examination for KF rings.

• #12 Wilson disease — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/wilson-disease/

  Wilson disease is diagnosed by specialist interpretation of clinical tests in the correct clinical context. Testing for the disease should be considered in: […] Tests to support the diagnosis of Wilson disease include: […] serum caeruloplasmin tests, where: very low serum-caeruloplasmin levels (0.1g/L) are highly suggestive of Wilson disease; […] urinary 24h copper collection, where: elevated 24-hour urinary copper levels (0.64mol/24-hour) are supportive of Wilson disease; […] slit lamp examination, where: Kayser-Fleischer rings are copper deposits at the periphery of the cornea, highly suggestive of Wilson disease; […] ATP7B gene sequencing. […] Other tests include: full blood count: thrombocytopaenia; […] liver function tests (all patterns of liver dysfunction possible), looking for: elevated bilirubin; elevated aminotransferases; elevated bilirubin:alkaline-phosphatase level; […] liver imaging for signs of cirrhosis/portal hypertension; […] magnetic resonance imaging of the brain (even in absence of neurological symptoms); […] liver biopsy with tissue copper quantification; and […] Leipzig scoring system (under specialist guidance).

• #13

  http://www.eurowilson.org/professional/diagnosis/index.phtml

  The diagnosis of WD is based on a combination of clinical, biochemical and genetic tests. […] Summary of tests performed for the diagnosis of Wilson disease 24 h urinary copper Serum copper Plasma caeruloplasmin Liver copper and histology Neuroimaging Molecular biology Clinical tests Scoring system Fulminant hepatic failure. […] The 24h urinary copper value may be misleading because of incorrect 24h urine collection, especially in pediatric patients, for whom 24h urine collection is not very easy. […] The total serum copper varies in different clinical scenarios in Wilson disease, because it may be low as a result of low caeruloplasmin, or elevated as a result of release of free copper from a damaged liver. […] Although, low plasma caeruloplasmin is reported in 73% of WD patients, false negatives have been observed in cases of infection, pregnancy and estrogens intake, because it is an acute phase reactant.

• #13

  http://www.eurowilson.org/professional/diagnosis/index.phtml

  Liver copper values equal to or higher than 250 g/gm of dry weight are considered to be the gold standard in the diagnosis of Wilson’s disease. […] Hepatic manifestations of Wilson disease are very similar to those observed in autoimmune hepatitis, steatosis, and fulminant hepatic failure. […] Neuroimaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, play an important role in the diagnosis of Wilson disease presenting neurologically. […] In recent years the developments of new techniques in genetic and molecular biology have provided useful tools in the diagnosis of Wilson disease. […] The diagnostic value of the KF ring is not the same for patients with neurological and hepatic disease. […] In 2001 at the 8th international conference on WD and Menkes disease a scoring system for the diagnosis of WD was discussed.

• #14 Wilson’s disease – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/wilsons-disease/

  Wilsons disease is diagnosed based on a combination of things including abnormal liver tests, clinical features such as signs of psychological or psychiatric illness, evidence of Kayser-Fleischer rings and genetic tests. You might have some or all of these things. […] A characteristic clinical sign of Wilsons disease is a rusty or coppery brown ring around your eye known as the Kayser-Fleischer ring (sometimes called the K-F ring). In most cases you cant see the ring with the naked eye. Around half of people with Wilsons disease have them. […] As part of testing for Wilsons disease you will have a slit-lamp eye examination to check for Kayser-Fleischer rings. A doctor who specialises in the diagnosis and treatment of eye conditions (ophthalmologist) will do the test. The slit-lamp is a type of specialised microscope with a high-intensity light beam attached that gives the doctor a very close-up view of your cornea.

• #15 Wilson’s Disease: Diagnosis and Treatment | Journal of Ethics | American Medical Association

  https://journalofethics.ama-assn.org/article/wilsons-disease-diagnosis-and-treatment/2003-04

  Wilson’s disease is an autosomal recessive disorder that results in copper accumulation and toxicity and occurs in about 1 out of every 40,000 people. […] The Kayser-Fleischer ring, a brownish-green discoloration from accumulation of copper granules deposited in the sclera at the periphery of the cornea, is virtually pathognomonic of Wilson’s disease. […] Positive screening test results include urine copper (over 100 micrograms/24 hour) and serum ceruloplasmin (below 5 milligrams/dl). For any patient in whom the diagnosis is not definitive, the gold standard is liver biopsy (over 2000 micrograms/g dry weight of tissue). […] Therefore, even though the disorder is rare, it is important to consider it in differential diagnosis, because failure to treat can lead to permanent damage including psychiatric and behavioral problems.

• #16 Wilson’s disease: diagnosis and management – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/wilsons-disease-diagnosis-and-management

  Wilson’s disease (WD) is a rare autosomal recessive genetic disorder characterised by the accumulation of copper in various body tissues, particularly the brain, liver and corneas of the eyes. […] Early diagnosis is important to avoid the possibility of permanent neurological dysfunction and serious liver disease. If a patient presents with any of the early symptoms of WD outlined above, pharmacists should refer them to secondary care for urgent blood tests to determine ceruloplasmin levels. […] Hepatologists, neurologists, ophthalmologists and nephrologists, usually in secondary care, will likely be involved in confirming the diagnosis, usually made when a combination of KF rings and a low serum ceruloplasmin (<0.1g/L) level is present. [...] Other tests include a 24-hour urinary copper (>1.6micromol/24 hours), serum ‘free’ copper (12.0–25.0 micromol/L), hepatic copper (>4micromol/g dry weight) and other liver function tests (e.g. serum aminotransferase).

• #17 Wilson Disease Workup: Approach Considerations, Serum Ceruloplasmin, Urinary Copper Excretion and Hepatic Copper Concentration

  https://emedicine.medscape.com/article/183456-workup

  This test is regarded as the criterion standard for diagnosis of Wilson disease. A liver biopsy with sufficient tissue reveals levels of more than 250 mcg/g of dry weight even in asymptomatic patients. […] The urinary copper excretion rate is greater than 100 mcg/d in most patients with symptomatic Wilson disease. The rate may also be elevated in other cholestatic liver diseases. […] The sensitivity and the specificity of this test are suboptimal for use as a screening test; however, it may be useful to confirm the diagnosis and to evaluate the response to chelation therapy. […] Radiolabeled copper testing directly assays hepatic copper metabolism. […] MRI of the brain appears to be more sensitive than CT scanning in detecting early lesions of Wilson disease. […] Positron emission tomography (PET) scanning reveals a significantly reduced regional cerebral metabolic rate of glucose consumption in the cerebellum, striatum, and, to a lesser extent, in the cortex and thalamus. […] The electron microscopic detection of copper-containing hepatocytic lysosomes is helpful in the diagnosis of the early stages of Wilson disease, in addition to the quantification of hepatic copper by atomic absorption spectrophotometry.

• #17 Wilson Disease Workup: Approach Considerations, Serum Ceruloplasmin, Urinary Copper Excretion and Hepatic Copper Concentration

  https://emedicine.medscape.com/article/183456-workup

  The presence of Kayser-Fleischer rings and ceruloplasmin levels of less than 20 mg/dL in a patient with neurologic signs or symptoms suggest a diagnosis of Wilson disease. If a patient is asymptomatic, exhibits isolated liver disease, and lacks corneal rings, the coexistence of a hepatic copper concentration of more than 250 mcg/g of dry weight and a low serum ceruloplasmin level is sufficient to establish a diagnosis. Therefore, in the absence of Kayser-Fleischer rings or neurologic abnormalities, a liver biopsy for quantitative copper determination is essential to establish the diagnosis of Wilson disease. […] Neurofilament light (NfL) may be a potential biomarker for neurologic involvement in Wilson disease, possibly guiding chelation therapy and investigations for novel therapies. […] Mutation analysis is an especially valuable diagnostic strategy for certain well-defined populations exhibiting a limited spectrum of ATP7B mutations.

• #18 Invitae Wilson Disease Test | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-06183

  The Invitae Wilson Disease Test analyzes the ATP7B gene, pathogenic variants in which can cause decreased biliary excretion of copper, reduced incorporation of copper into apoceruloplasmin, and the overall accumulation of copper in the body. […] Molecular genetics are necessary to confirm the diagnosis of Wilson disease. […] Affected individuals present with increased urinary copper excretion and low serum copper and ceruloplasmin levels. Molecular genetics are necessary to confirm a diagnosis of Wilson disease. […] For patients with clinical symptoms of Wilson disease, sequence variants in the gene ATP7B are identified in more than 98% of patients.

• #19 Wilson Disease: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/183456-overview

  Radiolabeled copper testing directly assays hepatic copper metabolism. […] Genetic testing is limited to screening of family members for an identified mutation detected in the index patient. […] Brain imaging shows characteristic findings; MRI appears to be more sensitive than CT in detecting early lesions. […] Abdominal imaging findings are neither sensitive nor specific. […] Resting ECG abnormalities include left ventricular or biventricular hypertrophy, early repolarization, ST segment depression, T-wave inversion, and various arrhythmias. […] Electron microscopic detection of copper-containing hepatocytic lysosomes is helpful in the diagnosis of the early stages of Wilson disease, in addition to the quantification of hepatic copper by atomic absorption spectrophotometry.

• #20 Wilson’s disease – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/wilsons-disease/

  You might have a liver biopsy to measure the amount of copper in your liver (hepatic copper concentration). Most people with Wilsons disease will have increased amounts of liver copper. […] Genetic testing is much more widely available in the past. You might have testing to check for the faulty gene that causes Wilsons disease, including an analysis that pinpoints the specific faults in the genes (molecular diagnosis). Very soon everyone with Wilsons disease will have a genetic analysis available. […] Commonly used imaging tests include: an MRI or CT scan of the part of the brain known as the basal ganglia, which is responsible for starting and controlling your bodys movements; MRI, CT, or ultrasound scan of your liver; a scan using transient elastography such as a Fibroscan to check your liver for scarring (fibrosis).

• #21 Wilson’s Disease – Zero To Finals

  https://zerotofinals.com/medicine/gastroenterology/wilsons/

  Wilson’s disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver. […] Serum caeruloplasmin is the initial screening test for suspected Wilson’s disease. A low serum caeruloplasmin is suggestive of Wilson’s disease. […] A 24-hour urine copper assay will show high urinary copper. […] Liver biopsy can be used to assess the liver copper content and assess liver disease. […] Scoring systems that consider various features and laboratory results are used to establish the diagnosis. […] Other investigations: Kayser-Fleischer rings on slit lamp examination, MRI brain may show changes, including the characteristic “double panda sign”, low haemoglobin with haemolytic anaemia (negative Coombs test), genetic testing (including screening family members).

• #22 New tools for Wilson’s disease diagnosis: exchangeable copper fraction

  https://atm.amegroups.org/article/view/24746/html

  Wilsons disease (WD) biochemical markers continue to evolve. Classical tests [serum copper, serum ceruloplasmin (Cp), urinary copper] have their own limits, and they are often insufficient to diagnose or exclude WD. […] Therefore, we focused our research on a direct measurement of serum copper labile fraction. Exchangeable copper (CuEXC) offers a correct view of the free copper overload. It provides information on the spread and severity of WD. Relative exchangeable copper (REC) (percentage of exchangeable to total serum copper) that appreciates the toxic fraction of copper in blood is an excellent biomarker for WD diagnosis. These two tests are reliable and non-invasive. They give rapid answers for an appropriate diagnosis and make possible to start the treatment quickly without waiting for the result of the genetic tests. As early diagnosis and treatment are the keystones of successful management of patients with WD, different teams have already applied these tests in a routine framework to a large number of patients.

• #22 New tools for Wilson’s disease diagnosis: exchangeable copper fraction

  https://atm.amegroups.org/article/view/24746/html

  The diagnosis is evoked on clinical symptoms and several biological tests: ceruloplasmin (Cp), serum and urinary copper concentrations, and sometimes calculated estimation of copper that is not bound to Cp. These determinations are often insufficient to diagnose or to exclude WD. […] However, early diagnosis and treatment are the keystones of the successful management of patients with WD. But thinking of a WD diagnosis is challenging as many patients have non-specific symptoms that precede those leading to the diagnosis. So, it is important to have a rapid, reliable, non-invasive and discriminative tool for the diagnosis of WD. It is why we developed the exchangeable copper (CuEXC) assay that leads to the calculation of the relative exchangeable copper (REC). […] Each isolated traditional biochemical marker is insufficient to set WD diagnosis. The association of the three biochemical markers (low serum Cp concentration, low serum copper concentration and high urinary copper excretion) is highly predictible of WD diagnosis.

• #23 New tools for Wilson’s disease diagnosis: exchangeable copper fraction

  https://atm.amegroups.org/article/view/24746/html

  CuEXC determination allows a direct an accurate measurement of copper overload. It provides, at diagnosis, information on the spread and severity of the disease. REC calculation (percentage of exchangeable to total serum copper) is a very valuable discriminative tool for WD diagnosis presenting excellent sensitivity and specificity. These two tests are rapid, reliable and non-invasive. Their routine uses, by different teams, in large cohorts of patients have been very successful and validated their important place as standard of care for WD patients. They give fast answers to an appropriate diagnosis and allow beginning quickly the treatment without waiting for genetic testing results.

• #24 Biochemical diagnosis of Wilson’s disease: an update

  https://www.degruyter.com/document/doi/10.1515/almed-2022-0020/html?lang=en

  Wilsons disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene. This paper reviews the diagnostic performance and limitations of the biochemical tests commonly used to detect this underdiagnosed disease. […] At present, a rapid, simple, reliable biochemical test that confirms diagnosis of WD is not available. However, diagnosis can be established based on serum ceruloplasmin and urinary copper excretion. Total serum copper should be employed with caution, since it has a low negative predictive value. […] Nevertheless, measured relative exchangeable copper has very high sensitivity and specificity and emerges as a potential gold standard for the biochemical diagnosis of WD. […] Currently, WD remains an underdiagnosed condition. Delayed diagnosis is the most common cause of severe complications and mortality.

• #24 Biochemical diagnosis of Wilson’s disease: an update

  https://www.degruyter.com/document/doi/10.1515/almed-2022-0020/html?lang=en

  Diagnosis of WD is challenging due to the lack of a rapid, simple, reliable, accurate test that is pathognomonic of the disease. On average, the time elapsed between the onset of symptoms and diagnosis exceeds two years, with a greater delay in patients with a neurological presentation. […] The algorithm proposed by AASLD is based on an initial ophthalmological screening for Kayser-Fleischer rings and on serum ceruloplasmin and urinary copper determination. […] The main limitations of the scoring system is that it is based on the opinions of a panel of experts instead of population-based studies, added to the lack of a standard ULR for urinary copper excretion. […] The studies assessing ceruloplasmin as a screening test for WD have been unsuccessful. These studies report a significant proportion of FNs due to ceruloplasmin being a positive acute phase reactant, and a high frequency of FPs, since a substantial number of neonates show low physiological ceruloplasmin concentrations.

• #25 Biochemical diagnosis of Wilson’s disease: an update

  https://www.degruyter.com/document/doi/10.1515/almed-2022-0020/html?lang=en

  A method has been recently developed by which ATP7B peptides in dried blood spot samples (heel prick test) are measured by tandem mass spectrometry after antibody-based enrichment. This method has a sensitivity of 91% and a specificity of 98% and shows promise as an avenue for including WD in newborn screening within the coming years.

• #26

  https://journals.lww.com/aomd/fulltext/2023/06030/diagnosis_and_management_of_wilson_s_disease_.1.aspx

  It should be noted that there is no single test for the diagnosis of WD. […] The sensitivity and specificity of these tests was observed to be low. […] A combination of clinical, radiology, and laboratory features can diagnose most patients with WD. […] Additional tests such as liver biopsy and genetics are required when the initial tests are indeterminate. […] Currently, genetic testing of the ATP7B gene is considered the gold standard for identifying mutations in molecular genetics. […] To aid diagnosis further, diagnostic criteria were developed at an international meeting in Leipzig, Germany, in 2001. […] This scoring system has been validated in adults and children (sensitivity 94.3%, specificity 94.4%, positive predictive value 90.9%, and negative predictive value 96.6%).

• #26

  https://journals.lww.com/aomd/fulltext/2023/06030/diagnosis_and_management_of_wilson_s_disease_.1.aspx

  The goal of treatment in WD depends on the symptomatic status of the patients. […] The initial goal of therapy is to increase urinary copper excretion from baseline levels (100 mcg/day). […] The rate of copper excretion decreases as copper stores get depleted. […] In presymptomatic patients, symptom onset should be prevented, and in first-degree family members, WD should be ruled out by mutational analysis. […] Previous studies suggest that clinically evident WD has an inevitably unfavorable outcome without treatment. […] Prompt and adequate treatment substantially improves survival, comparable to the general population. […] WD should be suspected in a young patient with movement disorders or psychiatric manifestations. […] The possible solution is to maintain a high degree of clinical suspicion for early diagnosis and adequate and monitored chelation.

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

  https://www.mdpi.com/2227-9059/9/9/1100

  A score ≥ 4 points would be confirmatory of WD, and this is already achievable if two deleterious mutations in ATP7B are detected segregating with the disease. […] Unfortunately, clinical assessment and other tests included in the Leipzig score not always yield clear findings, and genetic testing is not currently available in all settings. […] Ceruloplasmin (Cp) is a copper-binding protein responsible for 75–90% of the transport of this metal in blood. […] The predictive value of Cp as a unique marker for diagnosis of WD is questionable, principally because many WD patients show bordering levels. […] In treatment-naïve WD patients, urinary copper excretion (UCE), a reflection of serum NCC, is elevated, and thus, measure of copper in 24-h urinary collection is a common test for the diagnosis of WD.

• #28 Wilson Disease – Nutritional Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/nutritional-disorders/mineral-deficiency-and-toxicity/wilson-disease

  In Wilson disease, 24-hour urinary copper excretion (normally, 30 mcg/day) is usually 100 mcg/day. […] If serum ceruloplasmin is low and urinary copper excretion is high, diagnosis is clear. […] In unclear cases (eg, elevated transaminases, no Kayser-Fleischer rings, indeterminate values for ceruloplasmin and urinary copper), the diagnosis is made by doing a liver biopsy to measure hepatic copper concentration. […] Because early treatment is most effective, screening is indicated for anyone who has a sibling, cousin, or parent with Wilson disease. […] Screening consists of a slit-lamp examination and measurement of transaminase levels, serum copper and ceruloplasmin, and 24-hour urine copper excretion. […] If any results are abnormal, liver biopsy is done to measure hepatic copper concentration.

• #29 Wilson’s Disease (Hepatolenticular Degeneration) | Doctor

  https://patient.info/doctor/wilsons-disease-pro

  Liver biopsy is often diagnostic but is only required if clinical signs and non-invasive tests do not allow definitive diagnosis or if there is suspicion of additional liver pathology. […] Family screening of first-degree relatives should occur, as the chance of a sibling being homozygous (and therefore developing clinical symptoms) is 25%.

• #30 Wilson’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/wilsons-disease/symptoms-causes/syc-20353251

  Wilson’s disease is a rare inherited condition that causes copper levels to build up in several organs, especially the liver, brain and eyes. […] Ask your doctor whether you should have genetic testing to find out if you have Wilson’s disease. Diagnosing the condition as early as possible greatly increases the chances of successful treatment. […] Schilsky ML. Wilson disease: Diagnostic tests.

• #31 Challenges in the diagnosis of Wilson disease

  https://atm.amegroups.org/article/view/24633/html

  The challenge is to develop around the world this rapid and reliable biological test already practiced routinely in a dozen hospitals in France. […] The current challenge is to make NGS accessible widely around the world. […] Familial screening will have to be rethought and expanded because phenotypic expression is highly variable, even within the same family.

• #31 Challenges in the diagnosis of Wilson disease

  https://atm.amegroups.org/article/view/24633/html

  The understanding and management of Wilson disease (WD) have dramatically improved since the first description of the disease by K. Wilson more than a century ago. However, the persistent long delay between the first symptoms and diagnosis emphasizes challenges in diagnosing earlier this copper overload disorder. […] The most important challenge is to train physicians to recognize atypical or rare symptoms of WD that will lead to discuss the diagnosis more systematically. […] The second challenge is to confirm the diagnosis faster and more effectively so as not to delay the initiation of treatment, and expand family screening as the genetic prevalence is higher than previously expected. […] By drawing attention to the earliest and rare symptoms and to new biomarkers and diagnostic tools, we hope that this article will increase diagnostic awareness and reduce delays so that patients can start their treatment earlier in the course of the illness and thus have a better disease prognosis.

• #32 Biochemical diagnosis of Wilson’s disease: an update

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2022-0020/html?lang=en&srsltid=AfmBOooN0R0QdxnK3VKg0gHdP3vTYOYxWCE5_Bnn-AajFw_IuHSar_XE

  Wilsons disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene. This paper reviews the diagnostic performance and limitations of the biochemical tests commonly used to detect this underdiagnosed disease. […] At present, a rapid, simple, reliable biochemical test that confirms diagnosis of WD is not available. However, diagnosis can be established based on serum ceruloplasmin and urinary copper excretion. Total serum copper should be employed with caution, since it has a low negative predictive value. […] The development of novel assays for WD detection makes this disorder a potential candidate to be included in newborn screening programs. […] Diagnosis of WD is challenging due to the lack of a rapid, simple, reliable, accurate test that is pathognomonic of the disease. On average, the time elapsed between the onset of symptoms and diagnosis exceeds two years, with a greater delay in patients with a neurological presentation.

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