HHC/Wilson/A1AT

Question 1

AR hereditary liver disorder; body absorbs too much iron, which is then stored in the liver, skin, heart and pancreas; tissues with iron deposits take a red-orange hue; can result in fibrosis and cirrhosis; mutation in HFE gene (C282Y major, H63D minor)

Answer 1

Hereditary Hemochromatosis

Question 2

Mutations in Hereditary Hemochromatosis

Answer 2

On HFE gene: C282Y (major) and H63D (minor)

Question 3

(males/females) with hereditary Hemochromatosis usually present later in life with symptoms

Answer 3

Women: partially compensate with menstrual blood loss

Question 4

On MRI abdominal imaging, what can clue you in to Hemochromatosis

Answer 4

Very dark liver, heart and pancreas (iron deposits)

Spleen in lighter (no deposits)

Question 5

Histologic characteristics of Hemochromatosis

Answer 5

Periportal hepatocytes containing yellow-brown pigments (iron)

Question 6

Why might hepatocellular carcinoma in the setting of hereditary hemochromatosis NOT have iron accumulation in it’s cells

Answer 6

Hereditary Hemochromatosis is a life-long accumulation of iron (blue), but hepatocellular carcinoma (tumor cells) is not present long enough to accumulate iron.

Question 7

non-genetic mechanism for iron overload; usually seen with patients on chronic transfusion regimens (sickle cell disease, thalassemia, etc.)

Answer 7

Transfusion-associated iron overload

Question 8

In Hemochromatosis, iron deposits begin in _____________ cells and progress to hepatocytes

Answer 8

Kupffer (macrophages)

Question 9

Primary hemochromatosis

Transfusion Associated Iron Overload

Answer 9

Iron-induced reactive oxygen species

Question 10

Stain used to help diagnose Hemochromatosis (iron overload)

Answer 10

Prussian Blue stain

Question 11

How to treat/manage Hemochromatosis

Answer 11

Frequent phlebotomy
Fe chelation (SC anemia)

Question 12

How to diagnose Hemochromatosis

Answer 12

• Elevated transferrin/ferritin
• Genetic testing (Hereditary Hemochromatosis)
• Liver biopsy

Question 13

Signs/symptoms of Hemochromatosis (Hereditary or Transfusion)

Answer 13

Liver: Cirrhosis and HCC
Pancreas: Diabetes (damaged islet cells)
Reprod: Hypogonadism
Joints: Arthropathy
Skin: "Bronzing"
Heart: Cardiomyopathy

Question 14

AR genetic disorder of copper metabolism (unable to excrete in bile); accumulation in periportal hepatocytes, kidneys, brain, joints and cornea; can lead to hepatitis, liver failure and cirrhosis; mutation in ATP7B

Answer 14

Wilson’s Disease

Question 15

Mutation seen in Wilson’s Disease (copper retention)

Answer 15

ATP7B

Question 16

Normally, copper is excreted by the liver in the….

Answer 16

bile

Question 17

Patients with Wilson disease have low…

Answer 17

ceruloplasmin (protein that carries copper in blood) (less of it means more is stored in tissues and not excreted)

Question 18

Signs/Symptoms of Wilson’s Disease (copper retention)

Answer 18

Liver: hepatitis, cirrhosis and failure
Heme: hemolytic anemia
Neuro: psychosis, seizures, ataxia, tremors, behavior changes
Renal: proximal RTA, nephrolithiasis
Eyes: Kayser-Fleischer Rings (golden deposits around pupil)

Question 19

golden-brown deposits around pupil; seen in Wilson’s Disease (copper retention)

Answer 19

Kayser-Fleischer Rings

Question 20

How to diagnose Wilson’s Disease

Answer 20

High serum/urine copper (can’t excrete in bile)
Low serum ceruloplasmin
LOW alkaline phosphatase with HIGH total bilirubin

Question 21

If you see LOW alkaline phosphatase in the setting of HIGH total bilirubin, which liver disease should you think of?

Answer 21

Wilson’s Disease (copper retention)

Question 22

How to treat/manage Wilson’s Disease (copper retention)

Answer 22

Chelation (zinc, Trientine, etc.)
Liver transplant (for failure or cirrhosis)

Question 23

genetic metabolic disorder of the lungs and liver; mutation in SERPINA1 gene and A1AT protein (serine protease inhibitor); failure to secrete A1AT, causing an accumulation and polymerization in hepatocytes; causes lung disease due to less circulating A1AT

Answer 23

Alpha-1-Antitrypsin Deficiency

Question 24

Gene mutation associated with Alpha-1-Antitrypsin Deficiency

Answer 24

SERPINA1 gene

Question 25

Histology finding for Alpha-1-Antitrypsin deficiency

Answer 25

Eosinophilic PAS+ (Periodic Acid Schiff) granules

Question 26

How to diagnose Alpha-1-Antitrypsin Deficiency

Answer 26

Low serum A1AT

Genetic testing/phenotype