Wilson's disease and Haemochromatosis

Question 1

What is Wilson’s disease?

Answer 1

Excessive accumulation of copper in body tissues, particularly in the liver. It is AUTOSOMAL RECESSIVE

Question 2

What gene mutation causes Wilson’s disease?

Answer 2

ATP7B (the gene that provides the instructions for making a protein called copper-trasporting ATPase 2)

Question 3

How is copper normally excreted?

Answer 3

In bile

Question 4

Who does the symptoms of Wilson’s disease normally present in?

Answer 4

In teenagers or young adults (is rare to start after 40)

Question 5

When copper accumulates in the brain, what neurological symptoms can it cause?What does copper deposition in the basal ganglia cause?

Answer 5

Tremor
Dysarthria (speech difficulties)
Dystonia (abnormal muscle tone)
Dyskinesia (involuntary, erratic,writhing movements of the face, arms, legs or trunk)

Parkinsonism (a triad of tremors, bradykinesia and rigidity which are SYMMETRICAL)—> Is caused by copper deposits in the basal ganglia

Question 6

What psychiatric symptoms may patients develop with Wilson’s disease?

Answer 6

Abnormal behaviours, depression, cognitive impairment and psychosis (Wilson’s is very important to diagnose early and may be missed easily)

Question 7

What type of anaemia is usually associated with Wilson’s disease?

Answer 7

Haemolytic anaemia (low Hb levels caused by destruction of RBCs)

Question 8

Upon examining the eyes, what may be seen in a person with Wilson’s disease? What are they? What is the proper assessment to examine this feature of the eyes?

Answer 8

Kayser-Flesicher rings.
They are copper deposits in the Descemet’s membrane of the eyes. These are green-brown circles surrounding the iris of the eyes.

Proper assessment: Slit lamp examination

Question 9

How do you diagnose Wilson’s disease?

Answer 9

Serum ceruloplasmin is the initial screening tool for suspected Wilson’s disease. A LOW caeruloplasmin is suggestive of Wilson’s disease (it is the protein that carries copper in the blood).

However, it can be falsely normal or elevated in cancer or inflammatory conditions.

Question 10

What would a 24-hour urine copper assay show in someone with Wilson’s disease?

Answer 10

High urinary copper

Question 11

Apart from doing a serum caeruloplasmin test and 24-hour urinary copper assay, how else can you diagnose Wilson’s disease?

Answer 11

Lier biopsy (to assess liver copper content and liver disease)

Question 12

What findings may be seen on a T2 weighted MRI scan for someone who has Wilson’s disease?

Answer 12

Double panda sign (look at Notion notes)

Question 13

What happens to Hb with Wilson’s disease?

Answer 13

Low Hb with haemolytic anaemia (negative Coombs test)

Question 14

What can you do for the family members of those affected with Wilson’s including the pt?

Answer 14

Genetic testing

Question 15

How do you manage Wilson’s disease?

Answer 15

With copper chelating drugs. Examples are Penicillamine/ Trientine

Question 16

Apart from Penicillamine and trientine, what other drugs can be used to treat Wilson’s disease?

Answer 16

Zinc salts (they inhibit copper absorption in the GI tract)
Liver transplantation

Question 17

What is haemochromatosis?

Answer 17

An inherited disorder of iron metabolism in which intestinal iron absorption increases and leads to iron deposition in the joints, liver, heart,pancreas,pituitary,adrenals and skin.
It is an iron storage disorder

Question 18

Who tends to get more affected by hemochromatosis?

Answer 18

Middle-aged men. It presents more frequently and severely than in women (presents later in females due to menstruation acting to eliminate iron from the body regularly).

Question 19

Which gene is usually affected in the majority of cases of haemochromatosis?

Answer 19

C282Y mutations in the HFE (human haemochromatosis protein) gene which is located on chromosome 6.

Question 20

Is haemochromatosis an autosomal dominant or autosomal recessive condition?

Answer 20

Autosomal recessive

Question 21

What is the gene responsible for hereditary haemochromatosis? What are the 2 commonest gene mutations on this gene?

Answer 21

HFE (human haemochromatosis protein)

2 commonest mutations are C282Y and H63D.

C282Y accounts for 60-90% of HH
H63D accounts for 1-3% of HH

Question 22

How do patients present with haemochromatosis?

Answer 22

Chronic tiredness
Joint pain
Pigmentation (bronze skin)
Testicular atrophy
Erectile dysfunction
Amenorrhoea (absence of periods in women)
Cognitive symptoms (memory and mood disturbance)
Signs of chronic liver disease (hepatomegaly, cirrhosis)
Dilated cardiomyopathy

Question 23

What is the INITIAL investigation for haemochromatosis?

Answer 23

Measuring serum ferritin

Question 24

What are some causes of a raised ferritin?

Answer 24

Haemochromatosis
Infections (it is an acute phase reactant)
Chronic alcohol consumption
Non-alcoholic fatty liver disease
Hepatitis C
Cancer

Question 25

What blood investigations would you order for a patient with suspected haemochromatosis? What would be seen?

Answer 25

LFTs (is raised in HH)
Serum iron (raised ferritin and raised transferrin saturation although inflammation can also cause raised ferritin)

Question 26

How would you confirm a diagnosis of HH (hereditary hemochromatosis)?

Answer 26

Genetic testing for mutation in HFE gene (is used when BOTH the serum ferritin and transferrin saturations are in high)

Question 27

Apart from blood tests and genetic testing, what other investigations can be done for a patient with suspected hemochromatosis?

Answer 27

Liver biopsy (would see Perl’s stain. Quantify iron loading and assess disease severity)

It may also help stage the fibrosis and exclude other liver pathology

MRI (More specifically liver and cardiac.Can give a detailed picture and quantify the iron concentration in the liver)

Question 28

Between ferritin and transferrin, which is a better/more useful marker of HH?

Answer 28

Transferrin saturation

Although ferritin is the initial investigation, it can be raised in many other things like infections, NAFLD, hepatitis C, cancer,etc.

Question 29

What are the complications of haemochromatosis?

Answer 29

Secondary diabetes (iron affects the functioning of the pancreas)

Liver cirrhosis

Endocrine and sexual problems (hypogonadism, erectile dysfunction, amenorrhea and reduced fertility)

Cardiomyopathy (iron deposits in the heart)

Hepatocellular carcinoma

Hypothyroidism (iron deposits in the thyroid)

CHONDROCALCINOSIS (calcium pyrophosphate deposits in joints) causes arthritis

Question 30

What is the management plan for someone with hereditary haemochromatosis?

Answer 30

Venesection (regularly remove blood to remove excess iron-initially weekly)—> is FIRST-LINE

Monitoring serum ferritin

Monitoring and treating complications

Desferrioxamine —> SECOND-LINE