Inherited Conditions Flashcards by Zoe Tomlinson

What is haemochromatosis

iron storage disorder that results in excessive total body iron and deposition of iron in tissues

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Which gene is associated with haemochromatosis

human haemochromatosis protein (HFE) gene is located on chromosome 6
Auto-somal recessive

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When do symptoms of haemochromatosis generally begin

around age 40

- later in woman due to menstruation

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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)

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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

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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

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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

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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

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What is Wilson’s disease

excessive accumulation of copper in the body and tissues

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What gene is involved in Wilson’s Disease

“Wilson disease protein” on chromosome 13.
(ATP7B copper-binding protein)
Autosomal recessive

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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

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What neurological symptoms can occur due to Wilsons disease

Concentration and coordination difficulties
dysarthria (speech difficulties)
dystonia (abnormal muscle tone
Parkinsonism

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What are Kayser-Fleischer rings

deposition of copper in Descemet’s corneal membrane

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How do you diagnose Wilson’s disease

serum caeruloplasmin (low)
Low serum copper
Kayser-Fleischer rings
MRI brain shows nonspecific changes

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What is serum caeruloplasmin

protein that carries copper in the blood
can be falsely normal or elevated in cancer or inflammatory conditions
Not specific

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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.