Stage: 4: (Ministry of Education and Scientific Research) (Al-Muthanna University College of Medicine)
Stage: 4: (Ministry of Education and Scientific Research) (Al-Muthanna University College of Medicine)
Stage: 4: (Ministry of Education and Scientific Research) (Al-Muthanna University College of Medicine)
Stage : 4th.
Data: 2020/6/30
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Wilson Disease
Normally copper found in majority food like Like wheat, barley, legumes,
meats, shellfish, chocolate, and potatoes.
The standard approximate total body copper content is between 50 and
100 mg , and the average daily intake is between 1 and 5 mg.. It helps
maintain healthy bones, blood vessels, nerves, and immune function, and
it contributes to iron absorption. Copper is an important component of
several metabolic enzymes, including lysyl oxidase, cytochrome c oxidase,
superoxide dismutase, and dopamine beta-hydroxylase.
COPPER METABOLISM done by liver enzymes that excreted by bile with
feces about 90% and in urine about 10%.
In Wilson disease there is defect in excretion of copper by liver
metabolism.
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Epidemiology
The carrier frequency in the United States is 1 in every 90 individuals.
Wilson disease prevalence is 1 in every 30,000 individuals.
The prevalence of Wilson disease is between 10 and 30 million cases, and
the heterozygous carrier rate is 1 case per 100 individuals, with genetic
mutation rates ranging from 0.3% to 0.7%. In Japan the average is 1 case
per 30 000 men, compared to 1 case per 100 000 in Australia.
The increased frequency in certain countries is due to high rates of
consanguinity. The fulminant presentation of Wilson disease is more
common in females than in males.
A German study of patients with Wilson disease illustrated that patients
presenting earlier show predominantly hepatic symptoms , while those
presenting later more often present with neurological symptoms .
Age-related
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Pathophysiology
About 50% -75% of intestinal copper is absorbed and then transported
to the hepatocytes. In the case of Wilson disease this mechanism is
deterioration .
copper reaches the hepatocyte, it is incorporated into copper-
containing enzymes and copper-binding proteins (CBPs), including
ceruloplasmin, a serum ferroxidase.
Many of the gene defects for ATP7B , which response for formation
protein that Facilitates the linking process copper with cerulopalsmin,
lead to failure transporting .
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The excess copper resulting from Wilson disease promotes free radical
formation that results in oxidation of lipids and proteins. Ultrastructural
abnormalities in the earliest stages of hepatocellular injury, involving
the endoplasmic reticulum, mitochondria, peroxisomes, and nuclei,
have been identified. Initially, the excess copper accumulates in the
liver, leading to damage to hepatocytes. Eventually, as liver copper
levels increase, it increases in the circulation and is deposited in other
organs like basal ganglia of the brain, eyes, kidneys and skeleton.
Prognosis
Patients with a prognostic index (score) of 7 or greater should be
considered for liver transplantation.
All patient who exceeded this score died within 2 months of diagnosis.
Prognosis after liver transplantation is relatively good , the 1-year
survival rate was 79% and the overall survival rate was 72% at 3
months to 20 years.
Score 0 1 2 3 4
Serum bilirubin
(reference range, 3-20 < 100 100-150 151-200 201-300 >300
mmol/L)
Serum aspartate
transaminase (reference < 100 100-150 151-200 201-300 >300
range, 7-40 IU/L)
Prothrombin time
<4 4-8 9-12 13-20 >30
prolongation (seconds)
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Approach patient with Wilson disease.
Wilson disease has a variety of clinical manifestations, ranging from
asymptomatic to fulminating hepatic failure, chronic liver disease with
or without cirrhosis, neurological, and psychiatric.
Symptoms typically occur between age 5 and age 45. Hepatic disease
occurs primarily in infancy and early adolescence, though it may occur
in adults in their 50yrs .
ON HISTORY
1. Neurological symptoms : who present with neuropsychiatric
manifestations have cirrhosis . asymmetrical tremor difficulty speaking ,
excessive salivation, ataxia, and personality changes. Late
manifestations include dystonia, spasticity, grand mal seizures, rigidity,
and flexion contractures.
2. Musculoskeletal symptoms : osteopenia , Osteochondritis ,
chondromalacia and chondrocalcinosis have also been described.
3. Hematologic symptoms: Hemolytic anemia , hemolysis most often
occurs as a consequence of oxidative damage to the erythrocytes by the
higher copper concentration.
4. Renal symptoms: renal tubular damage, renal Fanconi syndrome
rarely presenting features.
on examination:
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Investigation
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Genetic Testing: Mutation analysis is a particularly valuable diagnostic
strategy for certain well-defined populations with a limited spectrum of
mutations with ATP7B.
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Treatment
chelating agent : nhibitor of copper absorption from the GI tract.,
reatment for patients who present with neurologic or psychiatric
manifestations.
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Reference
Schilsky ML. Wilson disease: current status and the future. Biochimie. 2009 Oct.
91(10):1278-81.
Kieffer DA, Medici V. Wilson disease: at the crossroads between genetics and
epigenetics-A review of the evidence. Liver Res. 2017 Sep. 1(2):121-30.
Bowcock AM, Farrer LA, Hebert JM, et al. Eight closely linked loci place the Wilson
disease locus within 13q14-q21. Am J Hum Genet. 1988 Nov. 43(5):664-74..
Stapelbroek JM, Bollen CW, van Amstel JK, et al. The H1069Q mutation in ATP7B is
associated with late and neurologic presentation in Wilson disease: results of a meta-
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Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD).
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disease: from west to east. Curr Neuropharmacol. 2016. 14(4):322-5.
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Weiss KH, Thurik F, Gotthardt DN, et al. Efficacy and safety of oral chelators in
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chelating agents in treatment of Wilson disease. Gastroenterology. 2011 Apr. 140(4):1189-
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da Costa Mdo D, Spitz M, Bacheschi LA, Leite CC, Lucato LT, Barbosa ER. Wilson's
disease: two treatment modalities. Correlations to pretreatment and posttreatment brain
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Brewer GJ, Askari F, Dick RB, et al. Treatment of Wilson's disease with
tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with
trientine. Transl Res. 2009 Aug. 154(2):70-7.
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