Wilson Disease

Question 1

Other name for Wilson disease ……?

Answer 1

Hepatolenticular degeneration

Question 2

Wilson disease associated with which system…..?

Answer 2

Liver disease,

Degenerative changes in the brain, and

Kayser-Fleischer (K-F) rings in the cornea

Question 3

Prompt diagnostic evaluation for Wilson disease should be done at what age of child presenting with liver disease……?

Answer 3

All patients over age 5 yr.

Question 4

Gene responsible for Wilson disease…….?

Answer 4

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.

Question 5

What happens if absence or malfunction of ATP7B results ……?

Answer 5

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

Question 6

Liver manifestations of Wilson disease…..?

Answer 6

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)

Question 7

At what age neurological manifestation occurs in Wilson disease……?

Answer 7

Liver disease is the most common disease
manifestation in children and can precede
neurologic symptoms by as long as 10 yr.

Question 8

Neurologic disorders in Wilson disease…….?

Answer 8

Intention tremor, dysarthria, rigid dystonia, Parkinsonism, choreiform movements, lack of motor coordination, deterioration in school performance, psychosis, or behavioral changes

Question 9

K F rings significance……?

Answer 9

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

Question 10

Psychiatric manifestations include in Wilson disease…….?

Answer 10

Depression, personality changes, anxiety, obsessive-compulsive behavior, or psychosis.

Question 11

Characteristics of Hemolytic anemia in Wilson disease…..?

Answer 11

Coombs-negative hemolytic anemia may be an initial manifestation, possibly related to the release of large amounts of copper from damaged hepatocytes

Question 12

Renal manifestations…..? Wilson Disease

Answer 12

Fanconi syndrome and progressive renal failure with alterations in tubular transport of amino acids, glucose, and uric acid may be present

Question 13

Unusual manifestations include in Wilson disease……?

Answer 13

Arthritis, pancreatitis, nephrolithiasis, infertility or recurrent miscarriages, cardiomyopathy, and hypoparathyroidism

Question 14

The earliest histologic feature of Wilson disease……?

Answer 14

Mild steatosis which may mimic nonalcoholic fatty liver disease or nonalcoholic steatohepatitis

Question 15

Indices of copper metabolism……?

Answer 15

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

Question 16

Serum ceruloplasmin levels should be interpreted with caution. Why…..?

Answer 16

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

Question 17

What is D penicillamine challenge test….?

Answer 17

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.

Question 18

About K F rings. …….?

Answer 18

Requires a slit-lamp examination by an ophthalmologist.

After adequate treatment, K-F rings resolve

Question 19

Role of liver biopsy in suspected Wilson disease…..?

Answer 19

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

Question 20

Hepatic copper accumulation…….?

Answer 20

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,

Question 21

How to screen for first degree relatives ….?

Answer 21

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

Question 22

Role of genetic screening in Wilson disease ….?

Answer 22

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

Question 23

Principles of management of Wilson disease….?

Answer 23

lifelong treatment should be initiated

Focused on limiting copper uptake and promoting

Copper excretion through dietary and pharmacologic measure

Question 24

Dietary copper restrictions in Wilson disease….?

Answer 24

The dietary intake of copper should be restricted to <1 mg/day

The normal diet contains 2-5 mg of copper per day.

Question 25

Copper containing foods …..…..?

Answer 25

High copper content foods such as liver, shellfish, nuts, and chocolate should be avoided

Question 26

Chelation therapy in Wilson disease…..?

Answer 26

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

Question 27

Response to chelation therapy in Wilson disease ….?

Answer 27

urinary copper excretion increases,

with marked improvement in hepatic and neurologic function and

the disappearance of K-F rings.

Question 28

Toxic effects of penicillamine therapy…..?

Answer 28

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

Question 29

Chelating agent under investigation for patients with neurologic disease ?…

Answer 29

Ammonium tetrathiomolybdate

Question 30

Role of zinc in Wilson disease management ……?

Answer 30

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.

Question 31

Adjuvant therapy in Wilson disease…..?

Answer 31

Antioxidants (vitamin E and curcumin) and pharmacologic chaperones (4-phenylbutyrate and curcumin) may have a role as adjunctive treatment but more research is needed.

Question 32

Prognosis of Wilson disease….?

Answer 32

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