Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Liver involvement may manifest as hepatitis, liver failure, or cirrhosis, while basal ganglia involvement causes the extrapyramidal signs. Most patients are diagnosed between the ages of 5 and 35 years (mean: 13 years). Diagnosis is established if the patient has low plasma ceruloplasmin, corneal deposits of copper (Kayser-Fleischer rings), and elevated copper levels in the urine. However, other tests are often needed since not all patients will have all these findings. The prognosis is good for patients without advanced liver disease and for those who are treated with the chelating agents penicillamine or trientine. Untreated Wilson disease is ultimately fatal, with patients dying from cirrhosis, acute liver failure, or complications due to progressive neurologic disease.
Worldwide prevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency: 1 per 30,000 live births, with many genetic variant mutations with different pathogenicities in the ATP7BgeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics
Typical age at onset is 5–35 years (mean age: 13 years)
Pathophysiology[1,4]
Normal copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements metabolism:
CopperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements is absorbed in the stomachStomachThe stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and duodenumDuodenumThe shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers.Small Intestine: Anatomy → binds to circulating albuminAlbuminSerum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood.Liver Function Tests → absorbed by various tissues
Excess copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements is excreted into the bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy → eliminated in feces
Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease is anautosomal recessiveAutosomal recessiveAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited.Autosomal Recessive and Autosomal Dominant Inheritance disorder caused by mutations in theATP7BgeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics found on chromosomeChromosomeIn a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.Basic Terms of Genetics 13.
Encodes a membrane-bound, copper-transporting ATPase
Regulates copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements transport within hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy
ATP7B protein deficiency or dysfunction causes the following:
Impaired excretion of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements into bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy → hepatic copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements accumulation → copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace ElementstoxicityToxicityDosage Calculation from oxidant damage to the liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
Decreased incorporation of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements into apoceruloplasminApoceruloplasminWilson Disease → copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements accumulates in tissues with low circulating levels of ceruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease (circulating copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements transport protein)
Different/variant mutations in the ATP7BgeneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics help explain some of the different clinical manifestations.
As the disease progresses, copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements accumulates in the following:
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
BrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification
CorneaCorneaThe transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye.Eye: Anatomy
KidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy
Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease usually presents in children and young adults. It rarely manifests after 40 years of age. Manifestations are primarily hepatic, neurologic, and psychiatric and may include:
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
Hepatomegaly +/– splenomegalySplenomegalySplenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
AscitesAscitesAscites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection).Ascites
Abdominal painPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
JaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
May include hepatitis, acute liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure, or cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
Kayser-Fleischer ringsKayser-Fleischer ringsCopper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris.Wilson Disease
CopperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements deposits in Descemet membrane of the corneaCorneaThe transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye.Eye: Anatomy, manifested as green-brown rings that encircle the iris
Present in:
> 90% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with neurologic or psychiatric presentations
50%–60% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with hepatic disease
Neurologic symptoms: Copper deposits within the brain cause extrapyramidal motor disturbances.
In the basal ganglia → wing-flapping tremor and parkinsonism-like symptoms (Note: The term “lenticular degeneration” used in the original description by Wilson, who was a medical student at the time, refers to the lenticular nucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles [putamen + globus pallidusGlobus pallidusThe representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus.Basal Ganglia: Anatomy] portion of the basal gangliaBasal GangliaBasal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy.)[3]
In the cerebellumCerebellumThe cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy → dysarthriaDysarthriaDisorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition.Wilson Disease,dysphagiaDysphagiaDysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, incoordination, and ataxiaAtaxiaImpairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions.Ataxia-telangiectasia
In the cerebrum → psychosis, dementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders, and affective disorder
Psychiatric symptoms: depression, irritability, or personality changes
Hemolytic disease: Coombs-negative hemolytic anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (HAHAHemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis).Hemolytic Anemia), often associated with jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice at presentation. Hemolytic anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types is commonly seen in acute liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure due to Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease, but it may also be seen without liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure as low-grade and chronic or episodic HAHAHemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis).Hemolytic Anemia.
Kayser-Fleischer ring: corneal copper deposition
Image: “Kayser-Fleischer rings” by Bentham Science Publishers, 2012. License: CC-BY-2.5
Mnemonic
Clinical presentation of Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease: ABCD
B: Basal gangliaBasal GangliaBasal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy degeneration symptoms (parkinsonismParkinsonismWest Nile Virus)
C: CirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis Corneal deposits (Kayser-Fleischer ring)
D: DementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders
Diagnosis
Considerations[6–8]
Testing for Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease should be considered in any patient with unexplained liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, neurologic, or psychiatric abnormalities, and 1st-degree relatives of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease should be screened for the disease.
Early diagnosis is crucial in order to prevent further disease complications.
Initial Workup[6,8]
Physical examination: Kayser-Fleischer ringsKayser-Fleischer ringsCopper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris.Wilson Disease are usually only seen with slit-lamp examinationSlit-Lamp ExaminationBlepharitis (present only in 50%–60% of those with isolated hepatic involvement, and in > 90% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with neurologic involvement).
Laboratory studies:
TransaminitisTransaminitisTick-borne Encephalitis Virus with ASTASTEnzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate.Liver Function Tests to ALTALTAn enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate.Liver Function Tests ratio > 2
↓ Serum ceruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease:[8]
CeruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease < 20 mg/dL (0.2 g/L)
CeruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease is an acute-phase protein; therefore, levels may be raised with intercurrent inflammatory illness.[6]
↑ CeruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease also noted in high-estrogen states: pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care, use of oral contraceptives, and estrogenEstrogenCompounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.Ovaries: Anatomy supplementation
Elevated 24-hour urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements excretion: 24-hour urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements > 40 µg/day or 0.6 µmol/day
CBC: AnemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types and hemolysis may be present.
In general, with physical exam and initial laboratory tests available:[8]
Unexplained liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease (+/– neuropsychiatric illness) with the following findings are diagnostic of Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease:[8]
Kayser-Fleischer ringsKayser-Fleischer ringsCopper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris.Wilson Disease
Low ceruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease
High urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements
Additional studies (see below) are needed if not all of the above findings are present.
Imaging[6–8]
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy ultrasound may show:
Hepatomegaly or splenomegalySplenomegalySplenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
Findings of cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
NeuroimagingNeuroimagingNon-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities.Febrile Infant should always be performed regardless of the presence of neurologic symptoms.[6]
To confirm the presence of cerebral copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements accumulation and basal nuclei damage
Ideally, MRI is performed (more sensitive in detecting lesions in the basal gangliaBasal GangliaBasal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy).
Gold standard tests:
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomybiopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma: increased copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements detected by quantitative assay (indicated if initial workup is indeterminate):[8]
CopperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements content ≥ 250 µg/g dry weight (normal, < 50 µg/g)
Note that elevated copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements content can also be found in chronic cholestasis (e.g., in primary biliary cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis).
Important to have at least 1–2 cm of biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma core length for analysis (as advanced liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease can have an inhomogeneous copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements content)
Due to the uneven distribution of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements in the liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy parenchyma in advanced stages, normal hepatic copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements content does not rule out disease.[6]
Other histologic findings (depending on stage of the disease) include steatosisSteatosisNonalcoholic Fatty Liver Disease, focal necrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage, glycogenated nuclei, hepatocellular degeneration.
Molecular genetic analysis:[8]
MutationMutationGenetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations analysis by whole-gene sequencing is possible.
Consider in cases of diagnostic uncertainty
The Leipzig criteria (calculator) were developed to assist in and standardize Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease diagnosis and management.[6]
Screen 1st-degree relatives of any patient newly diagnosed with Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease.
Include the following:
History relating to liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease, jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, and neurologic symptoms
Labs, including serum copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements, ceruloplasminCeruloplasminA multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation.Wilson Disease, liver function testsLiver function testsLiver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases.Liver Function Tests, albuminAlbuminSerum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood.Liver Function Tests, bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism, and basal 24-hour urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements
Treatment is initiated for those identified with the disease.
Management
Management may vary depending on practice location. The following information is based on US and European literature and guidelines for adult patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.
Lifestyle[6,8]
Low-copper diet: Avoid foods rich in copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements, such as organ meat, shellfish, nuts, and chocolate.
Once adherent to medical therapy, dietary restrictions may be unnecessary (with the exception of shellfish and liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy).
Avoid use of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements containers (for food) and cookware.
Medical management
Treatment requires lifelong pharmacotherapy.
Chelation of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements withpenicillaminePenicillamine3-mercapto-d-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in wilson’s disease.Wilson Diseaseor trientineTrientineAn ethylenediamine derivative used as stabilizer for epoxy resins, as ampholyte for isoelectric focusing and as chelating agent for copper in hepatolenticular degeneration.Antidotes of Common Poisonings (both inducing cupruria or urinary excretion of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements)[6–8]
PenicillaminePenicillamine3-mercapto-d-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in wilson’s disease.Wilson Disease side effects:
Allergic reactionsAllergic ReactionsType I hypersensitivity reaction against plasma proteins in donor bloodTransfusion Reactions (feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and rashRashRocky Mountain Spotted Fever)
LymphadenopathyLymphadenopathyLymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
BoneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow suppressionSuppressionDefense Mechanisms
Lupus-like syndrome
Renal dysfunction
Deterioration in neurologic state
TrientineTrientineAn ethylenediamine derivative used as stabilizer for epoxy resins, as ampholyte for isoelectric focusing and as chelating agent for copper in hepatolenticular degeneration.Antidotes of Common Poisonings side effects:
Autoimmune reactions
Renal dysfunction
BoneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow suppressionSuppressionDefense Mechanisms
Deterioration in neurologic state
Treatment monitoring:
Measure 24-hour urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements excretion while on treatment (adequate treatment → around 200–500 µg or 3–8 µmol/day on maintenance doseMaintenance DoseDosage Calculation).
Urinary copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements excretion may be higher when treatment is first started.
If 1st-line therapy is poorly tolerated: oral zincZincA metallic element of atomic number 30 and atomic weight 65. 38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol zn.Trace Elements (blocks intestinal absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements):[6,8]
Side effects:
StomachStomachThe stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy irritation
Changes in immune function
ZincZincA metallic element of atomic number 30 and atomic weight 65. 38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol zn.Trace Elements accumulation
Treatment monitoring:
Clinical and biochemical improvement
24-hour urinary excretion of copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements (should be < 75 µg or 1.2 µmol per 24 hours)
Table: Medications for Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease[6–8]
Medication
Typical dose (adults)
PenicillaminePenicillamine3-mercapto-d-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in wilson’s disease.Wilson Disease
125–250 mg/day
Increase by 250-mg increments every 7 days
Maximum: 1–1.5 g/day (2–4 divided doses)
TrientineTrientineAn ethylenediamine derivative used as stabilizer for epoxy resins, as ampholyte for isoelectric focusing and as chelating agent for copper in hepatolenticular degeneration.Antidotes of Common Poisonings
750–1250 mg/day (2–3 divided doses)
Maximum: 2 g/day
ZincZincA metallic element of atomic number 30 and atomic weight 65. 38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol zn.Trace Elements acetate
50 mg 3 times daily
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation[6–8]
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation may be required in severe cases, such as fulminant liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure or decompensated liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease despite medical therapy.
CopperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements metabolism normalizes.
The only rationale for discontinuing medical management
PrognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas[1]
Untreated Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease is fatal due to the continuous copperCopperA heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55.Trace Elements accumulation, with patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship dying from cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, acute liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure, or complications due to progressive neurologic disease.
The life expectancyLife expectancyBased on known statistical data, the number of years which any person of a given age may reasonably expected to live.Population Pyramids is unknown but is variableVariableVariables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups.Types of Variables. An approximate 5-year median survival after the appearance of neurologic symptoms was reported in one study. Of the patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship who develop acute liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure due to Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease, 95% die within days to weeks without liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation.
Survival with treatment is excellent, even in the presence of liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy damage (but not if the liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease is advanced). Lifelong treatment is required.
Huntington disease: can also present with neuropsychiatric manifestations in a patient < 40 years old. Symptoms include choreaChoreaInvoluntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases.Huntington Disease, athetosis, aggressionAggressionBehavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism.Oppositional Defiant Disorder, depression, and dementiaDementiaMajor neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide.Major Neurocognitive Disorders. Huntington diseaseHuntington diseaseHuntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs. Huntington Disease is caused by an autosomal dominantAutosomal dominantAutosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance trinucleotide repeat (CAG) in chromosomeChromosomeIn a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.Basic Terms of Genetics 4. BrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification imaging shows atrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation of the caudate and putamen. Kayser-Fleischer ringsKayser-Fleischer ringsCopper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris.Wilson Disease are not seen in Huntington diseaseHuntington diseaseHuntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs. Huntington Disease.
Parkinson disease: can also present with the following neuropsychiatric manifestations: pill-rolling tremorPill-Rolling TremorParkinson’s Disease, cogwheel rigidityCogwheel RigidityParkinson’s Disease, bradykinesiaBradykinesiaParkinson’s Disease, postural instability, and shuffling gaitGaitManner or style of walking.Neurological Examination. Parkinson diseaseParkinson diseaseParkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability.Parkinson’s Disease is associated with the loss of dopaminergic neuronsNeuronsThe basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.Nervous System: Histology of the substantia nigraSubstantia nigraThe black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis.Basal Ganglia: Anatomy. Histology shows deposits of α-synuclein (intracellular eosinophilic inclusions). Kayser-Fleischer ringsKayser-Fleischer ringsCopper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris.Wilson Disease are not seen in Parkinson diseaseParkinson diseaseParkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability.Parkinson’s Disease.
Hepatitis due to other causes (e.g., alcohol, acetaminophenAcetaminophenAcetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood.Acetaminophen): Neuropsychiatric manifestations of Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease help differentiate it from other causes of hepatitis (although hepatic encephalopathyHepatic EncephalopathyHepatic encephalopathy is a reversible condition in which elevated ammonia levels cause impaired brain function in patients with advanced liver disease. Hepatic encephalopathy can be precipitated by conditions that affect the normal absorption, metabolism, or clearance of ammonia, including dehydration, renal failure, infections, and gastrointestinal bleeding. Hepatic Encephalopathy can be associated with liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure). Clinical history, labs, and imaging can help differentiate causes of hepatitis from Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease.
Kasper, D. L., Braunwald, F. (2017). Harrison’s Principle of Internal Medicine (19th ed., vol. I, pp. 2519–2520).
Wilson, S. (1912) Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 34(4), 295–507. https://doi.org/10.1093/brain/34.4.295
Kumar, M., Gaharwar, U., Paul, S., et al. (2020) WilsonGen a comprehensive clinically annotated genomic variant resource for Wilson’s disease. Scientific Reports 10, 9037. https://doi.org/10.1038/s41598-020-66099-2
Hermann W. (2019). Classification and differential diagnosis of Wilson’s disease. Annals of Translational Medicine, 7(Suppl 2), S63. https://doi.org/10.21037/atm.2019.02.07
Kasztelan-Szczerbinska, B., Cichoz-Lach, H. (2021). Wilson’s disease: an update on the diagnostic workup and management. Journal of Clinical Medicine, 10(21), 5097. https://doi.org/10.3390/jcm10215097
European Association for Study of Liver. (2012). EASL clinical practice guidelines: Wilson’s disease. Journal of Hepatology, 56(3), 671–685. https://doi.org/10.1016/j.jhep.2011.11.007
Roberts, E. A., Schilsky, M. L., American Association for Study of Liver Diseases (AASLD). (2008). Diagnosis and treatment of Wilson disease: an update. Hepatology, 47(6), 2089–2111. https://doi.org/10.1002/hep.22261
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