Inherited Conditions Flashcards
What is haemochromatosis
iron storage disorder that results in excessive total body iron and deposition of iron in tissues
Which gene is associated with haemochromatosis
- human haemochromatosis protein (HFE) gene is located on chromosome 6
- Auto-somal recessive
When do symptoms of haemochromatosis generally begin
- around age 40
- later in woman due to menstruation
What are the symptoms of haemochromatosis
Chronic tiredness
Joint pain
Pigmentation (bronze / slate-grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
Investigations for haemochromatosis
- Serum ferritin
- transferrin saturation: To rule out ferritin as acute phase reactant
- Genetic testing if above are high
- Liver biopsy
- CT abdo/MRI
What stain is used in liver biopsy to test for Haemochromatosis
- Perl’s stain can be used to establish the iron concentration in the parenchymal cells
- used to be the gold standard
What are the complications of haemachromatosis
- Type 1 Diabetes
- Liver Cirrhosis
- Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)
- Cardiomyopathy
- Hepatocellular Carcinoma
- Hypothyroidism
- Chrondocalcinosis / pseudogout causing arthritis
What is the management of haemochromatosis
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
What gene is involved in Wilson’s Disease
- “Wilson disease protein” on chromosome 13.
- (ATP7B copper-binding protein)
- Autosomal recessive
What are the features of Wilson’s Disease
Hepatic problems (40%) Neurological problems (50%) Psychiatric problems (10%) Haemolytic anaemia Renal tubular damage leading to renal tubular acidosis Osteopenia
What neurological symptoms can occur due to Wilsons disease
- Concentration and coordination difficulties
- dysarthria (speech difficulties)
- dystonia (abnormal muscle tone
- Parkinsonism
What are Kayser-Fleischer rings
- deposition of copper in Descemet’s corneal membrane
-
How do you diagnose Wilson’s disease
- serum caeruloplasmin (low)
- Low serum copper
- Kayser-Fleischer rings
- MRI brain shows nonspecific changes
What is serum caeruloplasmin
- protein that carries copper in the blood
- can be falsely normal or elevated in cancer or inflammatory conditions
- Not specific
What is the management of Wilson’s
Copper chelation:
- Penicillamine
- Trientene
What is Alpha-1-antitrypsin deficiency
- Inherited deficiency of a protease inhibitor: alpha 1 antitrypsin
- excess of protease enzymes that attack the liver and lung tissue
- Autosomal recessive
- Chromosome 14
What is Alpha-1-antitrypsin (A1AT)
- Inhibits elastase, a enzyme secreted by neutraphils which digests connective tissue
How do you investigate for Alpha-1-antitrypsin
- Low serum alpha 1 anti-trypsin
- Liver biopsy: cirrhosis and acid-Schiff-positive staining globules in hepatocytes
- Genetic testing for the A1AT gene
- High resolution CT thorax diagnoses pulmonary emphysema
What is the management of Alpha-1-antitrypsin
- Stop smoking
- Symptomatic management
- Organ transplant for end stage liver or lung disease
- Monitoring for complications (e.g. hepatocellular carcinoma)
NICE recommend against the use of replacement alpha 1 antitrypsin, however the research and debate is ongoing regarding the possible benefits
What is primary biliary cirrhosis
- immune system attacks the small bile ducts within the liver causing obstruction of outflow of bile - cholestasis
- Back-pressure of the bile obstruction and the overall disease process ultimately leads to fibrosis, cirrhosis and liver failure.
Presentation of primary biliary sclerosis
Fatigue Pruritus GI disturbance and abdominal pain Jaundice Pale stools Xanthoma and xanthelasma Signs of cirrhosis and failure (e.g. ascites, splenomegaly, spider naevi)
What are the associations of Primary biliary cirrhosis
Middle aged women Other autoimmune diseases (e.g. thyroid, coeliac) Rheumatoid conditions (e.g. systemic sclerosis, Sjogrens and rheumatoid arthritis)
Investigations for primary biliary Cirrhosis
- LFTs: ALP raised initially then others
- Auto-antibodies
- ASR: raised
- IgM: raised
- Liver biopsy
What auto-antibodies are involved in primary biliary cirrhosis
- Anti-mitochondrial antibodies is the most specific to PBC and forms part of the diagnostic criteria
- Anti-nuclear antibodies are present in about 35% of patients
What is the treatment of primary biliary cirrhosis
- Ursodeoxycholic acid
- Colestyramine
- Liver transplant in end stage liver disease
- Immunosuppression (e.g. with steroids) is considered in some patients
What does ursodeoxycholic acid do
reduces the intestinal absorption of cholesterol
What does colestyramine do
a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
What are the complications of primary biliary cirrhosis
Symptomatic pruritus Fatigue Steatorrhoea (greasy stools due to lack of bile salts to digest fats) Distal renal tubular acidosis Hypothyroidism Osteoporosis Hepatocellular carcinoma
What is the disease progression in primary biliary cirrhosis
Disease course and symptoms vary significantly. Some people live decades without symptoms. The most important end results of the disease are advanced liver cirrhosis and portal hypertension.
What is primary sclerosing cholangitis
- intrahepatic or extrahepatic ducts become strictured and fibrotic causing an obstruction of bile flow
- Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts
What are the risk factors for primary sclerosing cholangitis
Male
Aged 30-40
Ulcerative Colitis
Family History
What is the presentation of primary sclerosing cholangitis
Jaundice Chronic right upper quadrant pain Pruritus Fatigue Hepatomegaly
What investigations should you complete for Primary sclerosing cholangitis
- LFTs: ALP > ALT
- Auto-antibodies: pANCA, ANA, aCL
Which autoantibodies are associated with primary sclerosing cholangitis
Antineutrophil cytoplasmic antibody (p-ANCA) in up to 94% Antinuclear antibodies (ANA) in up to 77% Anticardiolipin antibodies (aCL) in up to 63%
How do you diagnose primary sclerosing cholangitis
- MRCP: show bile duct lesions or strictures.
What are the associations and complications of primary sclerosing cholangitis
Acute bacterial cholangitis Cholangiocarcinoma: 10-20% of cases Colorectal cancer Cirrhosis and liver failure Biliary strictures Fat soluble vitamin deficiencies
What is the management of primary sclerosing cholangitis
- ERCP: dilate and stent any strictures
- Ursodeoxycholic acid i
- Colestyramine
- Liver transplant: curative but own problems
What is ERCP
inserting a camera through the persons throat, oesophagus, stomach and duodenum to the a point in the duodenum where the bile ducts empty into the GI tract. They then go through the sphincter of Oddi and into the ampulla of Vater. From the ampulla of Vater they can enter into the bile ducts and use X-rays and injecting contrast to identify any strictures. These strictures can then be dilated and stented during the same procedure providing improved flow through those ducts and an improvement in symptoms.
