Wilson Disease Flashcards
Other name for Wilson disease ……?
Hepatolenticular degeneration
Wilson disease associated with which system…..?
Liver disease,
Degenerative changes in the brain, and
Kayser-Fleischer (K-F) rings in the cornea
Prompt diagnostic evaluation for Wilson disease should be done at what age of child presenting with liver disease……?
All patients over age 5 yr.
Gene responsible for Wilson disease…….?
On Chromosome 13 (13q14.3), and encodes ATP7B, a copper transporting P-type adenosine triphosphatase (ATPase)
Which is mainly expressed in hepatocytes and is critical for biliary copper excretion and for copper incorporation into ceruloplasmin.
What happens if absence or malfunction of ATP7B results ……?
Decreased biliary copper excretion and diffuse accumulation of copper in the cytosol of hepatocytes.
With time, liver cells become overloaded and copper is redistributed to other tissues, including the brain and kidneys, causing toxicity, primarily as a potent inhibitor of enzymatic processe
Liver manifestations of Wilson disease…..?
asymptomatic hepatomegaly (with or without splenomegaly),
subacute or chronic hepatitis, and
acute hepatic failure (with or without hemolytic anemia)
Cryptogenic cirrhosis, portal hypertension, ascites, edema, variceal bleeding, or other effects of hepatic dysfunction (delayed puberty, amenorrhea, coagulation defects)
At what age neurological manifestation occurs in Wilson disease……?
Liver disease is the most common disease
manifestation in children and can precede
neurologic symptoms by as long as 10 yr.
Neurologic disorders in Wilson disease…….?
Intention tremor, dysarthria, rigid dystonia, Parkinsonism, choreiform movements, lack of motor coordination, deterioration in school performance, psychosis, or behavioral changes
K F rings significance……?
K-F rings are absent in young patients with hepatic Wilson disease up to 50% of the time
And these are present in 95% of patients with neurologic symptoms
Psychiatric manifestations include in Wilson disease…….?
Depression, personality changes, anxiety, obsessive-compulsive behavior, or psychosis.
Characteristics of Hemolytic anemia in Wilson disease…..?
Coombs-negative hemolytic anemia may be an initial manifestation, possibly related to the release of large amounts of copper from damaged hepatocytes
Renal manifestations…..? Wilson Disease
Fanconi syndrome and progressive renal failure with alterations in tubular transport of amino acids, glucose, and uric acid may be present
Unusual manifestations include in Wilson disease……?
Arthritis, pancreatitis, nephrolithiasis, infertility or recurrent miscarriages, cardiomyopathy, and hypoparathyroidism
The earliest histologic feature of Wilson disease……?
Mild steatosis which may mimic nonalcoholic fatty liver disease or nonalcoholic steatohepatitis
Indices of copper metabolism……?
Decreased serum ceruloplasmin levels (<20 mg/dL)
The serum free copper level may be elevated in early Wilson disease (>1.6 µmol/L)
urinary copper excretion (normally <40 µg/day) is increased to >100 µg/day and often up to 1,000 µg or more per day
Serum ceruloplasmin levels should be interpreted with caution. Why…..?
Acute inflammatory states and elevated estrogen levels (pregnancy, hormone therapy, or use of oral contraception) can falsely increase ceruloplasmin levels.
Additionally, serum ceruloplasmin may be low in autoimmune hepatitis, celiac disease, familial aceruloplasminemia, or in carriers of ATP7B mutations (mild variants of Menkes disease: occipital horn syndrome
What is D penicillamine challenge test….?
Prior to a 24 hr urine collection patients are given 2 500 mg oral doses of D-penicillamine 12 hr apart; affected patients excrete >1,600 µg/24 hr.
About K F rings. …….?
Requires a slit-lamp examination by an ophthalmologist.
After adequate treatment, K-F rings resolve
Role of liver biopsy in suspected Wilson disease…..?
Liver biopsy can determine the extent and severity of liver disease
And also for measuring the hepatic copper content (normally <10 µg/g dry weight)
It is only required if clinical signs and noninvasive tests do not allow a final diagnosis or if another liver disorder is suspected
Hepatic copper accumulation…….?
The hallmark of Wilson disease and measurement of hepatic parenchymal copper concentration is the method of choice for diagnosis.
Hepatic copper content >250 µg/g dry weight (>4 µmol/g dry weight) is the best biochemical evidence for Wilson disease,
How to screen for first degree relatives ….?
This screening should include determination of the serum ceruloplasmin level and 24-hr urinary copper excretion
If these results are abnormal or equivocal, liver biopsy should be carried
Role of genetic screening in Wilson disease ….?
Genetic screening by either linkage analysis or direct DNA mutation analysis is possible, especially if the mutation for the proband case is known or the patient is from an area where a specific mutation is prevalent, such as in central and eastern Europe where the H1069Q mutation is present in 50–80% of patients
Principles of management of Wilson disease….?
lifelong treatment should be initiated
Focused on limiting copper uptake and promoting
Copper excretion through dietary and pharmacologic measure
Dietary copper restrictions in Wilson disease….?
The dietary intake of copper should be restricted to <1 mg/day
The normal diet contains 2-5 mg of copper per day.
Copper containing foods …..…..?
High copper content foods such as liver, shellfish, nuts, and chocolate should be avoided
Chelation therapy in Wilson disease…..?
Oral administration of D-penicillamine (β,β-dimethylcysteine) in a dose of 1 g/day in 2 doses before meals for adults and 20 mg/kg/day for pediatric patients OR
Triethylene tetramine dihydrochloride (Trien, TETA, trientine) at a dose of 0.5-2.0 g/day for adults and 20 mg/kg/day for children
Response to chelation therapy in Wilson disease ….?
urinary copper excretion increases,
with marked improvement in hepatic and neurologic function and
the disappearance of K-F rings.
Toxic effects of penicillamine therapy…..?
Toxic effects of penicillamine occur in 10–20% and consist of hypersensitivity reactions (i.e., Goodpasture syndrome, systemic lupus erythematosus, and polymyositis), interaction with collagen and elastin, deficiency of other elements such as zinc, and aplastic anemia and nephrosis
Chelating agent under investigation for patients with neurologic disease ?…
Ammonium tetrathiomolybdate
Role of zinc in Wilson disease management ……?
Zinc has also been used as adjuvant therapy, maintenance therapy, or primary therapy in presymptomatic patients,
It’s unique ability to impair the gastrointestinal absorption of copper.
Zinc acetate can be given (adults) at a dose of 25-50 mg of elemental zinc 3 times a day, and 25 mg 3 times a day in children over age 5 yr.
Adjuvant therapy in Wilson disease…..?
Antioxidants (vitamin E and curcumin) and pharmacologic chaperones (4-phenylbutyrate and curcumin) may have a role as adjunctive treatment but more research is needed.
Prognosis of Wilson disease….?
Medical therapy is rarely effective in those presenting with acute liver failure
The prognosis for patients receiving prompt and continuous penicillamine is variable and depends on the time of initiation of and the individual response to chelation
Liver transplantation should be considered for patients with acute liver failure or decompensated cirrhosis due to Wilson disease
