Haemochromatosis Flashcards
What is hemochromatosis?
Is an iron storage disorder that results in excessive total body iron and deposition of iron in tissues.
What kind of genetic inheritance pattern does hemochromatosis follow?
It is an autosomal recessive inheritance. Caused by mutations in the HFE (human hemochromatosis protein) which is located on chromosome 6. The gene is important in regulating iron metabolism.
What are the symptoms of hemochromatosis?
Chronic tiredness
Joint pain
Pigmentation (bronze/state-grey discolouration
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
When does haemochromatosis usually present?
Haemochromatosis usually present after the age of 40 when the iron overload becomes symptomatic. It presents later in females due to menstruation acting to regularly eliminate iron from the body.
What is the main blood diagnosis approach for hemochromatosis?
The main diagnostic method is serum ferritin level.
Ferritin is an acute phase reactant, meaning that it goes up with inflammatory conditions such as infection.
Performing a transferrin saturation is helpful in distinguishing between a high ferritin caused by iron overload (transferrin saturation is high) from a high ferritin due to other causes such as inflammation or NAFLD.
If serum ferritin and transferrin saturation are high -> genetic testing is used to confirm
What are the complications of hemochromatosis?
Type 1 diabetes
Liver Cirrhosis
Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)
Cardiomyopathy
Hepatocellular carcinomaoma
Hypothyroidism
Chrondocalcinosis/pseudogout (calcium in joints) causing arthritis
What are the management options for hemochromatosis?
Venesection (weekly protocol of removing blood to decrease total iron)
Monitoring serum ferritin
Avoid alcohol
Genetic counseling
Monitoring and treatment of complications
What is Wilson’s disease?
Wilson’s disease is the excessive accumulation of copper in the body and tissues.
What is the genetic cuase of wilson’s disease?
It is caused by an autosomal recessive inheritance pattern. It is caused by a mutation in the Wilson disease protein or “ATP7B copper-binding protein” which is responsible for various functions, including the removal of excess copper in the liver, on chromosome 13.
What is the clinical presentation of Wilson’s disease?
Most patients with Wilson disease present with one or more of:
Hepatic problems (40%) - cirrhosis
Neurological problems (50%)
Psychiatric problems (10%)
What are the neurological symptoms of Wilson disease?
Neurological symptoms can be subtle and range from concentration and coordination difficulties to dysarthria (speech difficulties) and dystonia (abnormal muscle tone). Copper deposition in the basal ganglia leads to Parkinsonism (tremors, bradykinesia and rigidity). Motor symptoms are often asymmetrical in Wilson disease.
Kayser-Fleischer rings can be present in Wilson disease, what is it?
They are due to brownish circles surrounding the iris due to the deposition of copper in the descemet’s corneal membrane. They can usually be seen by the naked eye but proper assessment is made using slit lamp examination.
What other features may present in Wilson’s disease?
Haemolytic anaemia
Renal tubular damage leading to renal tubular acidosis
Osteopenia (loss of bone mineral density)
What is the diagnostic method for Wilson’s disease?
The initial choice is serum caeruoluplasmis - not specific as can be raised in cancer or inflammatory conditions.
A liver biopsy for copper content is the definitive gold standard test for diagnosis.
Can also be established if the 24 hour urine copper assay is sufficiently elevated
What is the treatment option for Wilson’s disease?
Treatment is with copper chelation using
- penicillamine
- trientine
