Wilson's disease and Haemochromatosis Flashcards
What is Wilson’s disease?
Excessive accumulation of copper in body tissues, particularly in the liver. It is AUTOSOMAL RECESSIVE
What gene mutation causes Wilson’s disease?
ATP7B (the gene that provides the instructions for making a protein called copper-trasporting ATPase 2)
How is copper normally excreted?
In bile
Who does the symptoms of Wilson’s disease normally present in?
In teenagers or young adults (is rare to start after 40)
When copper accumulates in the brain, what neurological symptoms can it cause?What does copper deposition in the basal ganglia cause?
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
What psychiatric symptoms may patients develop with Wilson’s disease?
Abnormal behaviours, depression, cognitive impairment and psychosis (Wilson’s is very important to diagnose early and may be missed easily)
What type of anaemia is usually associated with Wilson’s disease?
Haemolytic anaemia (low Hb levels caused by destruction of RBCs)
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?
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
How do you diagnose Wilson’s disease?
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.
What would a 24-hour urine copper assay show in someone with Wilson’s disease?
High urinary copper
Apart from doing a serum caeruloplasmin test and 24-hour urinary copper assay, how else can you diagnose Wilson’s disease?
Lier biopsy (to assess liver copper content and liver disease)
What findings may be seen on a T2 weighted MRI scan for someone who has Wilson’s disease?
Double panda sign (look at Notion notes)
What happens to Hb with Wilson’s disease?
Low Hb with haemolytic anaemia (negative Coombs test)
What can you do for the family members of those affected with Wilson’s including the pt?
Genetic testing
How do you manage Wilson’s disease?
With copper chelating drugs. Examples are Penicillamine/ Trientine
Apart from Penicillamine and trientine, what other drugs can be used to treat Wilson’s disease?
Zinc salts (they inhibit copper absorption in the GI tract)
Liver transplantation
What is haemochromatosis?
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
Who tends to get more affected by hemochromatosis?
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).
Which gene is usually affected in the majority of cases of haemochromatosis?
C282Y mutations in the HFE (human haemochromatosis protein) gene which is located on chromosome 6.
Is haemochromatosis an autosomal dominant or autosomal recessive condition?
Autosomal recessive
What is the gene responsible for hereditary haemochromatosis? What are the 2 commonest gene mutations on this gene?
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
How do patients present with haemochromatosis?
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
What is the INITIAL investigation for haemochromatosis?
Measuring serum ferritin
What are some causes of a raised ferritin?
Haemochromatosis
Infections (it is an acute phase reactant)
Chronic alcohol consumption
Non-alcoholic fatty liver disease
Hepatitis C
Cancer
What blood investigations would you order for a patient with suspected haemochromatosis? What would be seen?
LFTs (is raised in HH)
Serum iron (raised ferritin and raised transferrin saturation although inflammation can also cause raised ferritin)
How would you confirm a diagnosis of HH (hereditary hemochromatosis)?
Genetic testing for mutation in HFE gene (is used when BOTH the serum ferritin and transferrin saturations are in high)
Apart from blood tests and genetic testing, what other investigations can be done for a patient with suspected hemochromatosis?
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)
Between ferritin and transferrin, which is a better/more useful marker of HH?
Transferrin saturation
Although ferritin is the initial investigation, it can be raised in many other things like infections, NAFLD, hepatitis C, cancer,etc.
What are the complications of haemochromatosis?
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
What is the management plan for someone with hereditary haemochromatosis?
Venesection (regularly remove blood to remove excess iron-initially weekly)—> is FIRST-LINE
Monitoring serum ferritin
Monitoring and treating complications
Desferrioxamine —> SECOND-LINE
