Hereditary Haemochromatosis

Question 1

What is hereditary haemochromatosis (HH)?

Answer 1

An inherited disorder of iron metabolism.

There is increased intestinal iron absorption leading to iron depositions in many organs.

Question 2

Epidemiology of HH.

Answer 2

Middle-aged men are more frequently and severely affected than women.

In women the disease tends to present around 10 years later (this because menstrual blood loss is protective)

Question 3

Organs where depositions of iron are made.

Answer 3

Liver

Joints

Heart

Pancreas

Pituitary

Adrenals

Skin

Question 4

Genetics of HH.

Answer 4

One of the most common inherited conditions in those of northern european origin.

It is autosomal recessive.

Most HH are due to a mutation in HFE gene.

Hepcidin mutation can also cause it but this is rare.

Question 5

Early clinical features of HH.

Answer 5

Asymptomatic

Tiredness

Arthralgia of 2nd and 3rd MCP joints and knee pseudogout

Decreased libido

Question 6

Later clinical features of HH.

Answer 6

Slate-grey skin pigmentation

Signs of chronic liver disease

Hepatomegaly

Cirrhosis

Dilated cardiomyopathy

Question 7

Endocrinopathies related to HH.

Answer 7

DM (bronze diabetes from iron deposition in pancreas)

Hypogonadism due to decreased pituitary function

Question 8

Investigations in HH.

Answer 8

LFTs

Ferritin
Iron

Genotyping

Imaging

Liver biopsy

Question 9

Blood findings in HH.

Answer 9

Increased LFTs

Increased ferritin (inflammation also increases ferritin)

Increased transferrin saturation

HFE genotyping

Question 10

Imaging findings of HH.

Answer 10

Chondrocalcinosis

Liver and cardiac MRI can show FE overload

Question 11

Findings on liver biopsy.

Answer 11

Perl’s stain quantifies iron loading

This also assesses disease severity

Question 12

Types of management of HH.

Answer 12

Venesection

Monitoring

Over the counter drugs

Diet

Screening

Question 13

Explain venesection treatment in HH.

Answer 13

0.5-2 units of blood every 1-2 weeks.

This is until ferritin is less than 50 mcg/L - this can take as long as 2 years to achieve.

The iron will still accumulate so maintenance venesection is needed for life.

1 unit every 2-3 months to maintain haematocrit < 0.5, ferritin < 100mcg/L and transferrin saturation < 40%.

Question 14

What can be considered if the patient is intolerant to venesections?

Answer 14

Desferrioxamine (iron-chelating agent)

Question 15

Monitoring of HH.

Answer 15

LFTs and glucose/diabetes

HbA1c levels may be falsely low as venesection decreases the time available for Hb glycosylation so it is not reliable.

If cirrhotic screen for HCC by USS and AFP twice yearly

Question 16

Over the counter drugs in HH.

Answer 16

Ensure vitamin preparation contains no iron

Question 17

Diet management in HH.

Answer 17

Well-balanced diet

There is no need to avoid iron-rich foods

Avoid alcohol however

Avoid uncooked seafood (they may contain bacteria that thrive on increased plasma iron concentrations, such as L. monocytogenes and Vibrio vulnificus)

Question 18

Screening of HH.

Answer 18

Serum ferritin, transferrin saturation and HFE genotype.

All first degree relatives should be screened even if asymptomatic.

Question 19

Prognosis of HH.

Answer 19

Venesection treatment returns life expectancy to normal if non-diabetic and non-cirrhotic. This means that it is important to catch the disease early!

Arthropathy may improve or deteriorate

Gonadal insufficiency can reverse in young men

If cirrhotic 22-30% will develop HCC.

Increased risk with concurrent hepatitis, >50 yo, or alcohol

Question 20

Complications

Answer 20

Bronze Diabetes

Liver Cirrhosis

Hypogonadism, impotence, amenorrhea, infertility

Cardiomyopathy

HCC

Hypothyroidism

Chrondocalcinosis / pseudogout causing arthritis