Metabolic and genetic disorders of the liver

Question 2

Genetic metabolic liver disease - conditions

Answer 2

Hereditary hemochromatosis
Alpha-I antitrypsin deficiency (AATD)
Wilson disease
Gestational alloimmune liver disease (GALD)
Fatty acid oxidation defects
Glycogen storage deficiencies
Galactosemia
Lipid storage diseases
Tyrosinemia and urea cycle disorders
Peroxisomal disorders

Question 3

What is Haemochromatosis?

Answer 3

Excessive iron absorption
2 types: 1o hereditary autosomal recessive (C282Y) mutation in HFE
2o i.e. not genetic excessive intake

Question 4

symptoms of Haemochromatosis

Answer 4

Fatigue
Joint pain
Abdominal pain
Loss of libido
Fibrosis, cirrhosis
Cardiomyopathy
Bronze skin

Question 5

complications of haemochromatosis

Answer 5

Cirrhosis, cancer
Pancreas impaired
Arrythmia
Amenorrhea
Testicular atrophy
HPA impairment
Joint issues

Question 6

How to diagnose Haemochromatosis

Answer 6

↑ ↑ [iron]
↑ transferrin saturation
↑ [ferritin]
↓ total iron binding capacity
Biopsy – brown spots in hepatocytes

Question 7

Haemochromatosis treatments?

Answer 7

Deferoxamine chelating agent
Phlebotomy
Diet
Transplantation

Question 8

Gestational alloimmune liver disease (GALD)&raquo_space; Neonatal Hemochromatosis (NH)

Answer 8

• rare cond. during pregnancy
• Symptoms include include hypoglycemia, coagulopathy, hypoalbuminemia, elevated serum ferritin, elevated alpha-fetoprotein, and ascites

Question 9

Alpha-1 antitrypsin (AAT) deficiency

Answer 9

Alpha-1 antitrypsin (AAT) deficiency is a condition that raises your risk for lung and liver disease
AAT is a protein made in your liver to help protect the lungs&raquo_space; inactivates elastase (protease)
AAT deficiency&raquo_space; ↑ breakdown of elastin
Children with AAT deficiency often have liver disease poor appetite and fail to thrive.
Signs of liver damage include jaundice and swelling in your legs
In adults, the disease can present as lung disease
AAT deficiency respond well to asthma medicines. Some people can develop symptoms of COPD

Question 10

What is Wilson disease?

Answer 10

• inherited disorder
• excessive amounts of copper, in liver/ brain and eyes
• Excess copper is detrimental to the body because it can accumulate in the brain and liver where they generate free radicals, leading to neurological disorders or liver failure

Question 11

Wilson disease

Answer 11

Toxic effects of copper accumulation can lead to disabling physical symptoms, including:
characteristic brown ring around the cornea of the eye known as a Kayser-Fleischer ring
loss of muscle control and coordination
contractions and tremors
slowness of movement (bradykinesia)
inflammation, damage and in some cases scarring (fibrosis) in your liver. This is known as hepatitis. Some people with Wilson’s disease develop liver cirrhosis

Question 12

Treatment

Answer 12

The main treatments are medicines that stop copper building up
Chelation therapy: drugs D-penicillamine or trientine dihydrochloride (syprine) are given to remove copper from your body.
Some people may also need to change their diet, especially just after diagnosis, so they take in less copper from food.

Question 13

Management of Wilson disease

Answer 13

• transplantation in adults
• transplantation in children
• chelation therapy: penicllsmin monmotherapy 1st line

zinc salts

dietary copper restriction

Question 14

Monitoring and follow-up in Wilson disease

Answer 14

initial response to treatment = full BC
patient w neurological symptoms - regular

maintenance therapy 24hr urinasry copper outfop while cont. medications should be 3-8umol/day

risk of heptocellular carcinoma - HCC screening

family planning and preg - chelation therapy cont throughout pregnancy

women on chelating therapy should not be advised against breastfeeding

family screening; clinical assessment and getetic screening should be offered