Hemochromatosis

Question 1

pathophys

Answer 1

chronic inappropriate intestinal absorption due various hepcidin mutations (so without negative regulation of absorption, you have increased absorption)

Question 2

labs

Answer 2

• High transferrin sat (>50%)
• hyperferritinemia (>800)
• abnormal LFT’s

Question 3

presentation

Answer 3

EARLY: arthritis, depression
LATE: cirrhosis, HCC, DM2, hypogonadotropic hypogonadism, cardiomyopathy, increased skin melanization (most people don’t present with classic triad anymore due to widespread availability of genetic testing)

Question 4

treatment

Answer 4

• phlebotomy (*Mainstay)
• reduce vitamin c
• limit liver - toxicity (alcohol consumption)
• avoid raw shellfish
• pharmacologic chelation not generally indicated

Question 5

hemochromatosis means

Answer 5

iron overload

Question 6

2 main mechanisms of secondary hemochromatosis

Answer 6

• transfusion
• iron loading anemias (thalassemia, sideroblastic anemia, MDS) (due to increased iron absorption due to ineffective erythropoiesis)

Question 7

transferrin sat used as threshold to suggest hemochromatosis

Answer 7

50% or 45%?

Question 8

Most common forms of hereditary hemochromatosis

Answer 8

HFE hemochromatosis (most common)
TFR2 hemochromatosis

Question 9

Penetrance of HFE hemochromatosis

Answer 9

Low – so few people with the disease go on to develop overt iron overload

Question 10

Demographics

Answer 10

More likely males (testosterone suppresses hepcidin)

Question 11

How phlebotomy is typically done + goal of treatment

Answer 11

• “rapid depletional phase” (patients undergo phlebotomy every 2 weeks)
• then maintenance phase (monthly)
• goal = you want to phlebotomize aggressively and rapidly to prevent irreversible organ dysfunction

Question 12

General mechanism by which iron loading anemias lead to secondary hemochromatosis

Answer 12

• you have increased erythopoeisis despite it being ineffective —> this leads to decreased hepcidin production –> leading to increased iron absorption

Question 13

Number of transfusions it takes to develop transfusional iron overload

Answer 13

10-20

Question 14

Organs involved in transfusional iron overload in SCD

Answer 14

• liver
  *heart is spared in SCD for unclear reasons + endocrinopathies are less common

Question 15

Organs involved in secondary hemochromatosis in thalassemias

Answer 15

• liver
• cardiac
• endocrinopathies more common

Question 16

problem with using ferritin to monitor for transfusional iron overload

Answer 16

• doesn’t correlate well with liver iron (acute phase reactant)

Question 17

Better way to monitor for transfusional iron overload

Answer 17

Hepatic R2 and R2* MRI (correlates well with liver biopsy)

• annually
• can also do cardiac MRI

Question 18

ferritin goal with phlebotomy

Answer 18

less than 100

Question 19

FDA-approved iron chelators

Answer 19

• deferoxamine
• deferiprone
• deferasirox

Question 20

iron chelator typically used

Answer 20

deferasirox

Question 21

What are the iron loading anemias?

Answer 21

1) thalassemia
2) sideroblastic anemia
3) MDS

Question 22

Most common mutation in hereditary hemochromatosis

Answer 22

C282Y