Hereditary and congenital liver diseases Flashcards
What is the hallmark of hereditary haemochromatosis (HHC)
Systemic iron overload
What organs can be affected by iron overload
Liver pancreas heart joints pituitary
Mutations of what gene cause a defect in iron handling
The HHC gene (HFE)
Where is the class 1 protein, coded for by HFE expressed
Many cells including the duodenal crypts
What does the MHC protein interact with
The transferrin receptor to facilitate iron uptake into cells and defects in it alter this interaction
What type of condition is HHC
an autosomal dominant inherited condition
What type of condition is HHC
an autosomal dominant inherited condition
What is the prevalence of HHC in Caucasians
Between 1 in 300 to 1 in 400
What are the clinical features of HHC
Lethargy Abdominal pain (episodic) Hepatomegaly Chronic liver disease if advanced Diabetes
What coniditon is associated with iron overload and may occur in association with haemochromatosis
Porphyria cutanea tarda (PCT)
What are patients with iron overload at increased risk of
Yersinia enterocolitica infection
When might a false negative occur in blood tests for HHC
In menstruating women, ill patients, liver disease, hepatitis
What test has replaced liver biopsy in suspected iron overload
Genetic testing
What should be test for in genetic testing for HHC
C282Y and H63D
During screening of HHC, what should be acrried out
History and Examination
Transferrin saturation
Serum ferritin
What is the management of HHC
Venesection - at weekly intervals until the Hb concentration falls to normal.
Monitor the serum ferritin - keep value within the normal range
What is the prognosis of HHC like?
Dependent on the presence of cirrhosis or diabetes
Life expectancy is normal in the absence of this
What is Wilson’s disease
An autosomal recessive disorder caused by a defect in hepatic copper excretion resulting in copper overlaod and copper deposition in various organs which results in many abnormalities
What is the prevalence of Wilson’s disease
1 in 30000
How does copper accumulate in the liver in Wilson’s disease
It is not incorporated into its carrier protein, caeruloplasmin within hepatocytes and therefore is not adequately excreted into bile and accumulates in the liver
The abnormal genee for Wilson’s disease (ATP7B) is on which chromosome
Chromosome 13
How many copper binding sites are on the ATPase transporter
6
What might Wilson’s disease present as
Acute hepatitis Chronic liver disease Fulminant liver disease Progressive neurological disorder Pschiatric illness
At what age do patients usually become symptomatic
between 6 and 45
All patients being tested for autoimmune hepatitis should also be tested for what
Wilson’d disease
What is the hallmark of Wilson disease
A low caeruloplasmni
What is the main management for Wilson disease
Chelation therapy
Penicillamine which increases urinary excretion of copper
Pyridoxine is given in conjunction iwth penicillamine
Second line: Trientine
zinc
reduction of dietary copper
What is alpha 1 antitrypsin
A protease inhibitor that control tissue degradation by inhibiting a large number of proteases including trypsin, plasmin etc.
Where is alpha 1 antitrypsin produced
The liver
Where is alpha 1 antitrypsin produced
The liver
How does liver disease occur in alpha 1 antitrypsin deficiency
The accumulation of aggregated alpha 1 antitrypsin within the hepatocyte endoplasmic reticulum
Lung injury in alpha 1 antitrypsin deficiency is a result of what
Loss of protease inhibition
What is also associated with alpha 1 antitrypsin deficiency
COPD
How is COPD related to alpha 1 antitrypsin deficiency
It is due to the loss of the normal antiproteolytic defences against elastase
alpha 1 antitrypsin is encoded for by what
By a single gene located on chromosome 14
What are the clinical features of alpha 1 antitrypsin deficiency in childhood
Pruritus hepatomegaly conjugated hyperbilirubinaemia increased serum aminotransferase cholestasis can be marked
What happens to liver disease in alpha 1 antitrypsin deficiency in childhood
It often resolves spontaneously after 6 months
In adults with alpha 1 antitrypsin deficiency, what is there a high risk of
cirrhosis and HCC
How can alpha 1 antitrypsin deficiency be diagnosed
By a marked reduction or absence of the alpha-1- globulin band in an agarose gel electrophoresis
What is the management for alpha 1 antitrypsin deficient patients
Regularly assessed with LFT
Monitor for renal disease and vasculitis
CXR and pulmonary function assessmet
Smoking cessation
What can be given to patients with progressive emphysema and vasculitis
Purified human alpha 1 antitrypsin
What condiiton is associated with iron overload and may occur in association with haemochromatosis
Porphyria cutanea tarda (PCT)
During screening of HHC, what should be carried out
History and Examination
Transferrin saturation
Serum ferritin
What is Wilson’s disease
An autosomal recessive disorder caused by a defect in hepatic copper excretion resulting in copper overload and copper deposition in various organs which results in many abnormalities
All patients being tested for autoimmune hepatitis should also be tested for what
Wilson disease
What is the main management for Wilson disease
Chelation therapy
Penicillamine which increases urinary excretion of copper
Pyridoxine is given in conjunction with penicillamine
Second line: Trientine
zinc
reduction of dietary copper
What is the management for alpha 1 antitrypsin deficient patients
Regularly assessed with LFT
Monitor for renal disease and vasculitis
CXR and pulmonary function assessment
Smoking cessation
What can be given to patients with progressive emphysema and vasculitis
Purified human alpha 1 antitrypsin
What is Alagille’s syndrome
An inherited autosomal dominant disease causing cholestasis in conjunction with cardiovascular, facial, ocular, skeletal and neurodevelopmental abnormalities
What is another name for Alagille’s syndrome
Ateriohepatic dysplasia
What is the incidence of Alagille’s syndrome in Caucasia populations
1 in 100000 live births with no gender differences
What are the clinical features of Alagille’s syndrome
prolonged neonatal cholestasis
features of chronic liver disease, pruritus and xanthomata
What are some extrahepatic features of Alagille’s syndrome
Triangular face, broad forehead, saddle shaped nose, widely spaced deep set eyes, pointed chin butterfly vertebra renal abnormalities neurodevelopmental delay malnutrition and failure tot thrive
What are the investigations to determine Alagille’s syndrome
Liver biochemistry and bioosy \ cardiovascular testing renal function slit lamp eye examination spinal X rays serum bile acids cholesterol and triglycerides nutritional assessment
What is the management for patients with Alagille’s syndrome
Careful provision of adequate calories, protein and fat soluble vitamins
Management of mineral deficiencies
severe hyperlipidaemia - cholestryamine and ursodeoxycholic acid
Antihistamines for pruritus
What is the prognosis of Alagille’s sundrome
74% 10 year survival
What are the investigations to determine Alagille’s syndrome
Liver biochemistry and biopsy cardiovascular testing renal function slit lamp eye examination spinal X rays serum bile acids cholesterol and triglycerides nutritional assessment
What is the prognosis of Alagille’s sundrome
74% 10 year survival
What are autoimmune polyglandular sundromes
Autoimmune syndromes with symptoms affecting gland-bearing tissues and as such, the gut s often involved
What is the diagnosis of autoimmune polyglandular syndromes based on
The pattern of glandular disease
What are the porphyrias
Rare disorders of haem biosynthesis, characterised as either hepatic or erythropoeitic
What are the common environmental factors for causing symptoms of porphyrias
Alcohol
iron excess
oestrogens
hep C infection
What are the clinical features of porphyrias
Usually after puberty…
Photosensitive skin: pain, erythema bullae, hyperpigmentation
Acute relapsing -remitting neurological features : abdo pain
What are three of the main investigations required for porphyrias
Blood, Urine and stool investigations
What is the management for porphyrias
Avoid skin exposure and trauma : barrier creams
Avoidance of triggers
IV glucose
Administration of haem
What is biliary atresia
A very rare congenital condition of unknown cause in which there is obliteration or discontinuity of the extrahepatic biliary system
In which population is biliary atresia highest
Asian
What are the clinical features of Biliary atresia
Jaundice pale stools dark urine failure to thrive splenomegaly hepatomegaly
What are the 2 main groups of biliary atresia
Isolated biliary atresia (65-90%)
Associated situs inversus or polyspenia/aplenia with or without other congenital anomalies
What are the investigations involved for biliary atresia
Blood tests: Conjugater hyperbilirubinaemia
US to confirm diagnosis
Radioisotope scans of the liver
Liver biopsy
What is the management for Biliary atresia
Surgical reconstruction of the extrahepatic biliary tract is possible if the intrahepatic biliary tree is unaffected
If the atresia is complete - liver transplantation
