Haemochromatosis, Wilson's disease and Alpha 1 Antitrypsin Deficiency Flashcards
What is alpha-1-antitrypsin?
Protease inhibitor
Offers protection by inhibiting the neutrophil elastase enzyme (which digests connective tissues)
What organs are affected by alpha-1-antitrypsin deficiency?
Liver (cirrhosis after 50)
Lungs (bronchiectasis and emphysema after 30)
What chromosome codes for A1AT?
14
How does A1AT deficiency damage the liver?
alpha-1-antitrypsin created in liver
In deficiency, mutant version is created
This gets trapped in the liver, builds up, and causes liver damage
Liver damage progresses to cirrhosis over time
Can lead to hepatocellular carcinoma
How does A1AT deficiency damage the lungs?
Lack of A1AT leads to excess protease enzymes that attack connective tissue in the lungs
How is A1AT deficiency diagnosed?
Low serum-alpha 1-antitrypsin (screening test of choice)
Liver biopsy - cirrhosis and acid-Schiff-positive staining globules (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes
Genetic testing for the A1AT gene
High resolution CT thorax diagnoses bronchiectasis and emphysema
How is A1AT deficiency managed? (5)
Stop smoking
Symptomatic management
NICE recommend against the use of replacement alpha-1-antitrypsin
Organ transplant for end-stage liver or lung disease
Monitoring for complications (e.g. hepatocellular carcinoma)
What is haemochromatosis?
Iron storage disorder - results in excessive total body iron and deposition of iron in tissues
Majority of cases of haemochromatosis relate to mutations in human haemochromatosis protein (HFE) gene (C6)
Autosomal recessive
What are the symptoms of haemochromatosis?
Usually present 40 - iron overload becomes symptomatic
Later in females due to menstruation
Chronic tiredness
Joint pain
Pigmentation (bronze / slate-grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
How is haemochromatosis diagnosed?
Serum ferritin (but also acute phase reactant)
Transferrin saturation helps to distinguish between iron overload and high ferritin due to inflammation etc.
Genetic testing can be performed to confirm haemochromatosis
MRI looks at iron deposits in liver and heart
Complications of haemochromatosis (7)
Type 1 Diabetes (iron affects the functioning of the pancreas)
Liver Cirrhosis
Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)
Cardiomyopathy (iron deposits in the heart)
Hepatocellular Carcinoma
Hypothyroidism (iron deposits in the thyroid)
Chrondocalcinosis /
pseudogout (calcium deposits in joints) causing arthritis
Management of haemochromatosis (5)
Venesection (a weekly protocol of removing blood to decrease total iron)
Monitoring serum ferritin
Avoid alcohol
Genetic counselling
Monitoring and treatment of complications
What is Wilson’s disease?
Excessive accumulation of copper in the body and tissues
Mutation in “Wilson disease protein” on chromosome 13
Autosomal recessive
Features of Wilson’s disease
Hepatic problems (40%) Leads to chronic hepatitis and eventually liver cirrhosis
Neurological problems (50%)
Psychiatric problems (10%)
Haemolytic anaemia
Renal tubular damage leading to renal tubular acidosis
Osteopenia
What neurological symptoms occur with Wilson’s?
Range from concentration and coordination difficulties to dysarthria (speech difficulties) and dystonia (abnormal muscle tone)
Copper deposition in the basal ganglia leads to Parkinsonism (tremor, bradykinesia and rigidity)
Motor symptoms are often asymmetrical in Wilson disease
What psychological symptoms occur with Wilson’s?
Varies from mild depression to full psychosis
Underlying cause of Wilson disease is often missed and treatment delayed
Eye symptom in WIlson’s
Kayser-Fleischer rings in cornea (deposition of copper in Descemet’s corneal membrane)
How is Wilson’s disease diagnosed?
Serum caeruloplasmin - low is suggestive of Wilson’s
Can be falsely normal or elevated in cancer or inflammatory conditions
Liver biopsy is GOLD STANDARD
24-hour urine copper assay can also be used
Other investigations -
Low serum copper
Kayser-Fleischer rings
MRI brain shows nonspecific changes
What is the management of WIlson’s?
Treatment is with copper chelation using:
Penicillamine
Trientene
