Metabolic Diseases of the Liver

Question 1

List of metabolic diseases of the liver

Answer 1

A1AT deficiency, Wilson’s, NASH, Glycogen storage, Hereditary Hemochromatosis, Primary Hyperoxaluria, Familial amyloidosis, Gilbert, Criggler-Najjer, Dubin Johnson

Question 2

Characteristics of A1AT deficiency

Answer 2

• AR
• MM normal, ZZ and ZS alleles
• Mutated A1AT accumulates in liver = less circulating
• Destruction of CT matrix

Question 3

Clinical Features of A1AT deficiency

Answer 3

IN children, liver is more affected than lungs
- MC hereditary disorder in children
- elevated liver enzymes seen in 25% of patients
- neonatal jaundice, hepatomegaly, failure to thrive
- liver-related connections greater in children than adults
IN adults, lungs more affected than liver
- varying presentation lung>liver
- may have difficulties with COPD (chronic obstructive pulmonary disease), emphysema, chronic bronchitis, asthma, coughing, and repeated lung infections.
- ZZ liver has 8x greater risk of developing cirrhosis and 20x greater risk of HCC
- 80-90% of heterozygotes with cirrhosis or CLD have other identifiable cause

Question 4

Statistics of metabolic diseases

Answer 4

• accounts for 20% of orthotropic liver transplants in children
• 5% of adult liver transplantation due to HH/A1AT/WD

Question 5

Hepatic manifestations of systemic disease

Answer 5

NASH and Cirrhosis

Question 6

Diseases affecting the liver

Answer 6

Wilson’s, Hereditary Hemochromatosis, Glycogen Storage Disease

Question 7

Diseases from metabolic defects in the liver

Answer 7

Familial amyloidosis, primary hyperoxaluria

Question 8

How do metabolic disease cause harm to the liver?

Answer 8

Increased storage
- accumulation of metabolic products (fat)
- hepatomegaly and splenomegaly
- inflammation leading to fibrosis
- oncogenic pathway (tyrosinemia)
- susceptibility to infection (HH)
Metabolic failure
- hypoglycemia
- hyperammonia
- developmental delay

Question 9

General presentation of metabolic diseases of the liver

Answer 9

Huge variety

• developmental behavior delays
• dietary triggers
• family history
• birth history

Question 10

Signs of metabolic liver disease

Answer 10

dysmorphic features; unusual odours; cataracts; hepatosplenomegaly; cardiac dysfunction; ascites; abdominal distension; hypotonia; jaundice

Question 11

Symptoms of metabolic liver disease

Answer 11

hypoglycemia; acidosis; coagulopathy; ketosis; acute liver failure; recurrent vomiting; growth failure; neurological deterioration; coma; seizures; developmental delay

Question 12

Screening tests for metabolic diseases

Answer 12

Serum/Blood testing
- electrolytes, glucose, ammonia, amino acids, liver enzymes, lactate, pyruvate, ferritin and iron studies, peripheral smear
Urine Testing
- organic acids, orotic acids, reducing substances
Liver biopsy
Genetic Testing
Screening family members